Thalassemia - The Inherited Blood Disorder

Three people with inherited diseases successfully treated with CRISPR

2020-06-23T21:50:00.000+05:30

Sickle cell disease can distort red blood cells

Stocktrek Images, Inc/Alamy

Two people with beta thalassaemia and one with sickle cell disease no longer require blood transfusions, which are normally used to treat severe forms of these inherited diseases, after their bone marrow stem cells were gene-edited with CRISPR.

Result of this ongoing trial, which is the first to use CRISPR to treat inherited genetic disorders, were announced today at a virtual meeting of the European Hematology Association.

“The preliminary results… demonstrate, in essence, a functional cure for patients with beta thalassaemia and sickle cell disease,” team member Haydar Frangoul at Sarah Cannon Research Institute in Nashville, Tennessee, said in a statement.

Beta thalassaemia and sickle cell disease are conditions caused by mutations that affect haemoglobin, the protein that carries oxygen in red blood cells. Those with severe forms require regular blood transfusions.

However, a few people with the disease-causing mutations never show any symptoms, because they keep producing fetal haemoglobin in adulthood. Normally, fetal haemoglobin stops being produced soon after birth.

This discovery has inspired the development of treatments based on boosting fetal haemoglobin. In this trial, run by collaborating companies CRISPR Therapeutics and Vertex, bone marrow stem cells are removed from people and the gene that turns off fetal haemoglobin production is disabled with CRISPR.

The remaining bone marrow cells are killed by chemotherapy, then replaced by edited cells. This is done to ensure that new blood cells are produced by the edited stem cells, but the chemotherapy can have serious side effects including infertility.

The first two patients with beta thalassaemia no longer need blood transfusions since being treated 15 and five months ago. Nor does the patient with sickle cell disease, nine months after treatment.

The results are excellent, says Marina Cavazzana at the Necker-Enfants Malades Hospital in Paris, France, whose team has treated a 13-year-old boy with sickle cell disease using a different approach.

Although the three patients did experience some adverse effects due to the chemotherapy, the CRISPR gene editing appears safe. However, the patients may need to be monitored for the rest of their lives to be sure it has no adverse effects, says Cavazzana.

Altogether five people have now been treated. The trial was put on hold because of the coronavirus pandemic, but has now resumed.

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Are patients with thalassemia more susceptible to serious COVID-19 disease?

2020-06-22T22:05:00.002+05:30

COVID-19 and Thalassemia: Frequently Asked Questions

(last updated June 8, 2020)

Input from Drs. Maria Cappellini, Antonio Piga, Janet Kwiatkowski and Alexis Thompson

Note: Please review ASH's disclaimer regarding the use of the following information.

Are patients with thalassemia more susceptible to serious COVID-19 disease? Does splenectomy confer a higher risk?

Thalassemia patients, especially young adults/adults, have a chronic condition which may be associated with several co-morbidities linked to the underlying disease as well as complications of chronic transfusions, including heart failure, pulmonary hypertension, and diabetes. Thus, it seems possible that there could be an increased risk of more severe COVID-19 disease in some patients. Nonetheless, outcomes were recently reported from a small cohort of Italian patients followed in the northern part of Italy, where the pandemic has been the most widespread, showing most experienced relatively mild to moderate COVID-19 disease.¹ The number of infected thalassemia patients was lower than expected, likely due to earlier and more vigilant self-isolation compared to the general population.

Splenectomy is not known to increase the general risk of viral infection or severe viral disease, but no specific data exists for SARS-CoV-2. Splenectomized patients who develop fever should be evaluated for possible bacterial infection and should receive antibiotics to cover secondary bacterial infections.

Should any changes in transfusion schedules or thresholds be made in the context of the COVID-19 pandemic?

At present there is no evidence that the SARS-CoV-2 virus may be transmitted through donated blood. It is advisable to maintain the individual’s chronic transfusion regimen. Clinics and infusion centers should offer patients the safest possible environment for receiving transfusions, in areas free of COVID-19 patients or those being screened for respiratory symptoms and providing health care personnel protective equipment.

Hematologists and other thalassemia care providers should continue to follow local and national developments related to possible blood shortages related to COVID-19. Clinical sites and blood banks should develop contingency plans for adjusting transfusion regimens and obtaining appropriate donor units for individuals with alloimmunization in the event a significant shortage develops.

Should thalassemia patients continue iron chelation if they are exposed to or have confirmed COVID-19 disease?

No data are available regarding iron chelation and susceptibility to COVID-19 or severity of infection. If a patient is exposed but asymptomatic there is no reason to interrupt iron chelation. If a patient becomes symptomatic, particularly with moderate to severe disease, then interruption of iron chelation is advisable, with ongoing communication between the treating physicians and the hematologist.

Many comorbidities in thalassemia are related to iron overload. Patients should be reminded that adherence to the iron chelation dose and schedule recommended by their thalassemia care provider will reduce organ injury and thalassemia complications.

What about treatment with the recently approved disease-modifying drug luspatercept during the COVID-19 pandemic?

Luspatercept has been approved for adults with transfusion dependent beta thalassemia and has been shown to significantly reduce transfusion burden in this population. No data are available to date on luspatercept and COVID-19. If patients are currently taking luspatercept, there are no theoretical reasons to stop treatment. If the drug has decreased transfusion frequency, then continuing treatment would be beneficial in terms of avoiding prolonged clinic visits for transfusions and decreasing utilization of a limited blood supply.

What are the recommendations for stem cell transplantation or gene therapy for thalassemia during the COVID pandemic?

Due to high risk of infection in hospital settings and the risk of myeloablation, most allogeneic stem cell transplantation and gene therapies were postponed during the initial phases of the pandemic. In localities with a fall in COVID-19 hospitalizations, patients and their physicians can begin to discuss moving forward with planned procedures, particularly in patients with gene therapy cell products already prepared or with limited allogeneic donor availability. There is no evidence that SARS-CoV-2 can be transmitted via hematopoietic stem cell grafts.

References

Motta et al, Am J Hematol, 2020 SARS‐CoV‐2 infection in beta thalassemia: preliminary data from the Italian experience. https://doi.org/10.1002/ajh.25840
Karimi M, et al. Prevalence and Mortality due to Outbreak of Novel Coronavirus Disease (COVID-19) in β-Thalassemias: The Nationwide Iranian Experience. Br J Haematol. 2020 Jun 2.
Roy NBA, et al. Protecting vulnerable patients with inherited anaemias from unnecessary death during the COVID-19 pandemic. Br J Haematol. 2020 May;189(4):635-639.

For additional information, see:

Resources for providers to share with their patients
- Cooley Anemia Foundation
- Thalassemia International Federation

Public Health Webinar Series on Blood Disorders

2020-06-22T21:53:00.003+05:30

CDC’s Division of Blood Disorders (DBD) is proud to offer its Public Health Webinar Series on Blood Disorders. The purpose of this series is to provide evidence-based information on new research, interventions, emerging issues of interest in blood disorders, as well as innovative approaches in collaborations and partnerships. We invite you to join us in this series.

Archives for 2020

Sujit Sheth, MD
Harold Weill Professor, Chief of Pediatric Hematology and Oncology, and Vice Chair for Clinical Research, Department of Pediatrics, Weill Cornell Medicine

Director, New York Comprehensive Thalassemia Center, New York-Presbyterian Hospital/Weill Cornell Medical Center

Overview of Novel Thalassemia Treatments

The thalassemia syndromes are among the most common genetic disorders. Homozygous or compound heterozygotes have a wide spectrum of clinical severity, with the most severe requiring regular blood transfusions to maintain health and prevent morbidity. Transfusion-associated iron overload and its complications result in significant morbidity and mortality, thus disease-modifying treatments are a major unmet need in the management of these individuals.

During the past five years, novel approaches to treatment have been possible with advances in technology. In this webinar, Dr. Sheth will discuss the basic pathophysiology of the disease and specific targets for novel therapies. He will review data from trials of the newer agents aimed at reducing or abolishing the transfusion burden and mention additional strategies that are in early stage development that have the potential to completely change the landscape of thalassemia care.

Longer Life Expectancy is Possible for Some Sickle Cell Disease Patients, Case Study Contends

2016-10-12T22:17:00.003+05:30

By Alice Melao

A published case study reports that patients with mildly symptomatic sickle cell disease (SCD) can exceed the U.S. median life expectancy of 47 years for patients with the disease if it is managed properly.

The report published in Blood, the Journal of the American Society of Hematology, “Case series of octogenarians with sickle cell disease,” analyzes four women diagnosed with milder forms of SCD who have lived as long as 86 years.

“For those with mild forms of SCD, these women show that lifestyle modifications may improve disease outcomes,” stated Samir K. Ballas, MD, professor emeritus in the Department of Medicine at Sidney Kimmel Medical College at Thomas Jefferson University in Philadelphia, and principal author of the case study.

Ballas went on to explain that strong and long-term family support are important factors for the reported long life expectancy and high quality of life of the SCD patients. Moreover, strict adherence to medication and appointments also were reported as being highly important for the disease outcome.

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“It is very likely that their healthy lifestyles were important contributors to their longevity,” said Ballas. “All of the women were non-smokers who consumed little to no alcohol and maintained a normal body mass index. This was coupled with a strong compliance to their treatment regimens and excellent family support at home,” he said.

The four cases studied in this report were considered by Ballas to be “desirable” disease states. “These women never had a stroke, never had recurrent acute chest syndrome, had a relatively high fetal hemoglobin count [which helps to prevent cells from sickling], and had infrequent painful crises. Patients like this usually — but not always — experience relatively mild SCD, and they live longer with better quality of life,” Ballas said.

Nevertheless, Ballas points out that this study included only four participants and all were women. Given so, more studies with a broader group of study is still required.

In summary, Ballas is hopeful that the stories of these four women can serve as examples for SCD patients. “I would often come out to the waiting room and find these ladies talking with other SCD patients, and I could tell that they gave others hope, that just because they have SCD does not mean that they are doomed to die by their 40s — that if they take care of themselves, and live closely with those who can help keep them well, that there is hope for them to lead long, full lives,” the author concluded.

Promising Gene Therapy For Sickle Cell Ready for Clinical Trial

2016-10-01T21:32:00.001+05:30

By Alexandra Anderson PhD

A new engineered gene therapy virus, inserted into blood stem cells and then transplanted into mice with sickle cell disease, markedly reduced red blood cell damage according to the study “Lineage-specific BCL11A knockdown circumvents toxicities and reverses sickle phenotype,” published in theJournal of Clinical Investigation.

A clinical gene therapy trial is expected in the coming year in which researchers will use a gene manipulated harmless virus to prevent the “sickling” of red blood cells. The new gene therapy is based on research going back to the 1980s which revealed that people with a milder form of sickle cell disease carried a fetal form of hemoglobin.

Hope and Destiny: The Patient and Parent's Guide to Sickle Cell Disease and Sickle Cell Trait
This form is present in the human fetus and normally tapers off after birth. It differs most from “adult” (beta) hemoglobin because it is able to bind oxygen to a larger extent and is not seen to “sickle”.

In later studies, Dana-Farber/Boston Children’s Cancer and Blood Disorders Center researchers showed that suppressing a gene (BCL11A) that acts as an “off-switch” on the fetus hemoglobin, could restart the production again. With this approach the team was able to replace much of adult hemoglobin with the fetus form, in mice with sickle cell disease.

Dr. David A. Williams and colleagues from the center later adopted the approach.

“BCL11A represses fetal hemoglobin and also activates ‘adult’ hemoglobin, which is affected by the sickle-cell mutation,” Williams, the study’s senior author, said in a news release. “So when you knock BCL11A down, you simultaneously increase fetal hemoglobin and repress sickling hemoglobin, which is why we think this is the best approach to gene therapy in sickle cell disease.”

The new team tried to turn this insight into a therapy approach but they faced a problem. They discovered that the BCL11A gene also plays an important role in blood stem cells — which caused serious problems with the general blood development.

After some engineering in which the team used different gene techniques to silence the “switch-off” gene, without influencing the general blood development, they inserted the whole package into a lentivirus made for safe use in humans. Blood stem cells treated with this gene therapy were then successfully transplanted into mice and reduced the signs of sickle cell disease.

Additionally, in red blood cells from mice and four patients with the disease, the fetal hemoglobin surpassed the sickling “adult” hemoglobin, making up at least 80 percent of the total hemoglobin in the cell. According to the researchers, these results are more than enough to avoid the disease.

Williams believes this gene therapy approach will substantially increase the ratio of non-sickling versus sickling hemoglobin in patients, and his team is now taking the final steps toward FDA clearance for a clinical gene-therapy trial in sickle cell disease, that is expected to begin in early 2017.

New Biophysical Markers Could Help Develop Treatments for Sickle Cell Disease

2016-09-27T22:53:00.000+05:30

by Dr. Trupti Shirole

Sickle cell disease is an inherited blood disorder that affects an estimated 80,000 to 100,000 Americans each year. People with sickle cell disease have an abnormal form of hemoglobin, a protein found in red blood cells that carry oxygen throughout the body.

Normal red blood cells are flexible discs that easily bend and stretch to flow through the body's narrow blood vessels. In sickle cell disease, the abnormal hemoglobin forms fibers that cause the blood cells to take on a flattened, sickled shape and stiffen when they lose oxygen. This change in shape and rigidity causes the red blood cells to be stuck in the blood vessels and prevents the transport of oxygen to the surrounding tissue. This can cause anemia and extreme pain and impact the health of the body's tissue and organs.

Currently, hydroxyurea is the only FDA-approved drug for sickle cell disease. The drug reduces sickling in red blood cells and is used to treat pain and reduce the need for blood transfusions in some patients, but it does not work in all patients. Researchers have been divided over what mechanisms cause the drug to work. Some believe it works by reactivating fetal hemoglobin, which is better at transporting oxygen than the abnormal hemoglobin that causes sickling. Others believe it works by increasing the volume of red blood cells, reducing the concentration of sickle hemoglobin.
An interdisciplinary, international group of researchers has found new biophysical markers that could help improve the understanding of treatments for sickle cell disease, a step toward developing better methods for treating the inherited blood disorder.

"There is a critical need for patient-specific biomarkers that can be used to assess the effectiveness of treatments for sickle cell disease," said Subra Suresh, president of Carnegie Mellon University and co-author of the study. "This study shows how techniques commonly used in engineering and physics can help us to better understand how the red blood cells in people with sickle cell disease react to treatment, which could lead to improved diagnostics and therapies."

The findings from engineers, physicists and clinicians from Carnegie Mellon, the University of Pittsburgh, the Massachusetts Institute of Technology, Florida Atlantic University, Korea University, the Korea Advanced Institute of Science and Technology, and Harvard University will be published this week in the online early edition of the Proceedings of the National Academy of Sciences (PNAS).

In the current study, the international research team evaluated the biophysical properties - shape, surface area and volume - and biomechanical properties - flexibility and stickiness - of red blood cells under normal oxygenated conditions using electromagnetic waves to measure small differences in physical properties. The technique, known as common-path interferometric microscopy, allowed researchers to get a three-dimensional view of the cells.

Using blood samples from patients with sickle cell disease, the researchers separated red blood cells into four groups based on their density. Normal, disc-shaped red blood cells were the least dense, while severely sickled cells were the most dense. They then took samples from people receiving hydroxyurea treatment and those not receiving treatment. The red blood cells of those receiving treatment showed an improvement in all of the biophysical and biomechanical properties tested across all density levels. Furthermore, improvement in the physical properties of red blood cells of people treated with hydroxyurea correlated more with an increase in the red blood cell volume than with levels of fetal hemoglobin.

"Our findings shine a light on the mechanism behind hydroxyurea action, which has long been debated in the scientific community," said Ming Dao, principal research scientist in MIT's Department of Materials Science and Engineering and co-author of the study. "It's exciting to see that using the latest optical imaging tools, we can now confirm which one is the dominating mechanism. Understanding the key mechanism of action will allow us to explore novel and improved therapeutic approaches for sickle cell disease."

The researchers hope that these biophysical markers can be combined with biochemical and molecular-level markers to assess things like the severity of a patient's sickle cell disease, determine whether or not a patient will respond to hydroxyurea treatment and monitor the effectiveness of that treatment.

Sickle Cell Natural Healing: A Mother's Journey
Source: Eurekalert

Gene editing of blood stem cells can correct disease-causing mutations

2016-09-23T23:34:00.003+05:30

Recent advances in gene editing technology, which allows for targeted repair of disease-causing mutations, can be applied to hematopoietic stem cells with the potential to cure a variety of hereditary and congenital diseases. Gene editing can overcome many of the obstacles associated with gene addition therapies, but this young field still faces many challenges before it is ready for human testing, as discussed in a Review article published in Human Gene Therapy.

The article entitled "Gene Editing of Human Hematopoietic Stem and Progenitor Cells: Promise and Potential Hurdles" is part of a special joint issue on stem cell gene therapy in Human Gene Therapy and Stem Cells & Development guest edited by Luigi Naldini, MD, Scientific Director, San Raffaele Telethon Institute for Gene Therapy, Milan, Italy. A special "upside-down" print issue will be distributed at ESGCT/ISSCR Florence 2016 in October.
Gene Editing, Epigenetic, Cloning and Therapy

Kyung-Rok Yu, Hannah Natanson, and Cynthia Dunbar, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, describe how earlier gene addition strategies and the hurdles they encountered have informed the current development of gene editing approaches. The authors present the state-of-the-art in gene editing technology and the potential to apply these novel techniques to repair genetic flaws in hematopoietic stem cells, which give rise to the different types of cells in blood, and then to test those strategies in human clinical trials.
"Gene editing is the hottest new technology in gene therapy. The use of this approach to genetically modify hematopoietic stem and progenitor cells is very promising, but requires a careful assessment," says Editor-in-Chief Terence R. Flotte, MD, Celia and Isaac Haidak Professor of Medical Education and Dean, Provost, and Executive Deputy Chancellor, University of Massachusetts Medical School, Worcester, MA. "This mini-review by Dr. Dunbar's group at NIH provides a very insightful analysis of recent advances and current limitations of this approach

Smartphone App may offer needle free way to screen Blood for Anemia

2016-09-21T22:30:00.002+05:30

Carolina Henriques:

Engineers and computer scientists from the University of Washington (UW) have developed what they are calling a HemaApp, designed to detect hemoglobin concentration using simply a smartphone camera and a little extra lighting — rather than needles or an expensive, specialized machine.

Measuring hemoglobin, a protein found in red blood cells, is particularly important for people with anemia and other blood disorders, who require frequent blood draws. The app is also thought to detect abnormal hemoglobin properties, which could help screen for diseases such as sickle cell anemia.

Described in an article that won a ‘Best Paper’ award, HemaApp will be presented at the Association for Computing Machinery’s 2016 International Joint Conference on Pervasive and Ubiquitous Computing (UbiComp 2016), taking place on Sept. 15 in Germany.

Healthcare providers now measure hemoglobin levels by drawing blood with a needle or an intravenous line, or by using Masimo Pronto, an U.S. Food and Drug Administration (FDA)-approved device that measures hemoglobin noninvasively by clipping a sensor onto a person’s finger. The device, however, is too expensive for many medical facilities worldwide.

“In developing countries, community health workers have so much specialized equipment to monitor different conditions that they literally have whole bags full of devices,” Edward Wang, the study’s lead author and UW electrical engineering doctoral student, said in a press release. “We are trying to make these screening tools work on one ubiquitous platform — a smartphone.”

HemaApp works by analyzing the color of blood when light is shone from the phone’s camera — with a little help, for now, from external lighting — through a patient’s fingers, and then estimating hemoglobin concentrations. By analyzing how colors are absorbed and reflected across wavelengths, it can detect concentrations of hemoglobin and other components, like plasma.

HemaApp was tested in an initial trial including 31 patients. Requiring only one smartphone modification, HemaApp performed as well as the Masimo Pronto, the researchers said.

To make sure that the technology works on different skin tones and body masses, the team developed processing algorithms that use the patient’s pulse to differentiate between the properties of the patient’s blood and the physical aspects of the patient’s finger.

The UW team tested the app under three different scenarios: using the smartphone camera’s flash alone, in combination with a common incandescent lightbulb, and with a low-cost LED lighting attachment – additional light sources fall onto other sections of the electromagnetic spectrum that aren’t now found on all smartphone cameras.

“New phones are beginning to have more advanced infrared and multi-color LED capabilities,” said Shwetak Patel, the paper’s senior author and an endowed professor in Computer Science and Engineering and Electrical Engineering at UW. “But what we found is that even if your phone doesn’t have all that, you can put your finger near an external light source like a common lightbulb and boost the accuracy rates.”

In the initial studies, HemaApp’s hemoglobin measurements had a 69% correlation to a patient’s complete blood count (CBC) test, a 74% correlation when using a common incandescent light bulb, and an 82% correlation using a small circle of LED lights attached to the phone. Masimo Pronto scored an 81% correlation to the blood test.

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The app is not meant to replace blood tests, but results suggest that it could be an effective and affordable screening tool to determine if blood testing is needed. When used in anemia screening, HemaApp accurately identified 79% of the cases of low hemoglobin levels and 86% when aided with light sources.

“Anemia is one of the most common problems affecting adults and children worldwide,” said Doug Hawkins, a UW Medicine, Seattle Children’s Hospital, and Seattle Cancer Care Alliance pediatric cancer specialist. “The ability to screen quickly with a smartphone-based test could be a huge improvement to delivering care in limited-resource environments.”

MegaFood - Blood Builder, Promotes Healthy Blood Cell Production & Circulation, 90 Tablets (Premium Packaging) Further research steps include further testing of HemaApp to collect additional data and improve accuracy rates. The research project received financial assistance from the Washington Research Foundation.

Stem cell transplant cures children with sickle cell anemia, says Alberta hospital

2016-09-21T22:04:00.000+05:30

7 girls, 2 boys cured in what lead doctor considers unprecedented treatment

By Lisa Monforton,

Cardelia Fox has a tattoo on the inside of her right forearm with the words "Set free."

It's a reminder of how a cutting-edge transplant at the Alberta Children's Hospital cured her of sickle cell anemia and a life of hospital stays and blood transfusions.

The chronic genetic blood disorder caused Fox to have three childhood strokes — the first when she was only six months old. She would have two more at age six and 10.

Until the age of 17, she had been in and out of hospital and previously needed to have monthly life-saving blood transfusions.

The year Fox turned 17 she was one of the first patients to undergo the stem cell transplant procedure at the Alberta Children's Hospital.

The success of the procedure has captured interest from around the world, says Dr. Greg Guilcher, a pediatric oncologist who leads the sickle cell blood and marrow transplant program in Calgary.

Dr. Greg Guilcher is the lead doctor for the stem cell transplant procedure at Alberta Children's Hospital.

"To our knowledge, no one else is offering this protocol in children with sickle cell anemia," said Guilcher, who is also an assistant professor in the departments of oncology and pediatrics at the University of Calgary's Cumming School of Medicine.

What sets the Calgary procedure apart from other sickle cell anemia cures in young children is the lead up to the transplant.

"This protocol uses the 'lightest' doses of medication — no chemotherapy but immune suppressing drugs only, with a low dose of radiation," said Dr. Guilcher in a statement.

While the protocol was developed and is used in the U.S., Dr. Guilcher said he's not aware of any other hospital using it on children.

More exciting is the fact that there have been no incidents of stem cell rejection.

"We're getting phone calls and emails from around the world from interested parents and other doctors. We think we're ahead of the curve in offering this curative therapy as a standard of care."

Sickle cell anemia is a chronic illness where blood vessels can become blocked when blood cells change into a sickle shape, potentially affecting every organ and causing strokes, lung disease heart strain and spleen and bone damage. With advanced drug therapy treatment, life expectancy is 55- to 60-years-old.

The success of the procedure, which was first performed in Calgary in 2009, has cured seven girls and two boys to date.

Life-changing, says patient

"Before the stem cell transplant I felt like I was trapped," says Fox, whose sister Tamika Allen was a perfect match — a rare one in five occurrence within families. "Without this treatment I would likely still be at Foothills getting blood transfusions every month."

Tamika Allen, left, was a perfect stem cell match to her sister Cardelia Fox, which allowed her to have a procedure curing her of sickle cell anemia. (CBC)

Once Allen found out she was a full match, she didn't think twice about helping her sister.

Without a family match, the transplant procedure is generally considered too risky to perform.

"When we learned I was a match there was never any question of whether or not I'd do it," said Tamika, now 22. "Of course I'm going to do this for my sister. It was such a good feeling to be able to help make her life better — now I call her my mini-me."

Rising incidence in Canada

People of African descent are most often affected by sickle cell anemia. One parent can pass on the mutation and not cause the illness, but the illness results when both parents pass it on.

Fox's grandmother died at the age of 35 because of complications from the disease.

In 2008, the Sickle Cell Clinic at the children's hospital regularly treated 16 children.

Now there are more than 80, primarily because of immigration, says Dr. Mike Leaker. He is the head of the clinic, which sees patients from Alberta, Saskatchewan and eastern B.C.

"We now have some excellent medications that can change the course of the illness for many patients," said Leaker. "But a drug is still a treatment, not a cure. For families the word 'cure' is incredibly powerful."

Guilcher is expecting continued interest in the procedure from around the world

Sickle Cell Anemia: From Basic Science to Clinical Practice

Cure for sickle cell in adults validated

2016-09-17T22:07:00.000+05:30

Source:: University of Illinois at Chicago
Summary:: Physicians have cured 12 adult patients of sickle cell disease using a unique procedure for stem cell transplantation from healthy, tissue-matched siblings. The new technique eliminates the need for chemotherapy to prepare the patient to receive the transplanted cells and offers the prospect of cure for tens of thousands of adults suffering from sickle cell disease.

Ieshea Thomas was the first adult to be cured of sickle cell disease with the chemotherapy-free procedure at UI Health.

Credit: Image courtesy of University of Illinois at Chicago

Physicians at the University of Illinois Hospital & Health Sciences System have cured 12 adult patients of sickle cell disease using a unique procedure for stem cell transplantation from healthy, tissue-matched siblings.

The transplants were the first to be performed outside of the National Institutes of Health campus in Maryland, where the procedure was developed. Physicians there have treated 30 patients, with an 87 percent success rate. The results of the phase I/II clinical trial at UI Health, in which 92 percent of treated patients were cured, are published online in the journal Biology of Blood & Marrow Transplantation.
The new technique eliminates the need for chemotherapy to prepare the patient to receive the transplanted cells and offers the prospect of cure for tens of thousands of adults suffering from sickle cell disease.
About 90 percent of the approximately 450 patients who have received stem cell transplants for sickle cell disease have been children. Chemotherapy has been considered too risky for adult patients, who are often more weakened than children by the disease.
"Adults with sickle cell disease are now living on average until about age 50 with blood transfusions and drugs to help with pain crises, but their quality of life can be very low," says Dr. Damiano Rondelli, chief of hematology/oncology and director of the blood and marrow transplant program at UI Health, and corresponding author on the paper.
"Now, with this chemotherapy-free transplant, we are curing adults with sickle cell disease, and we see that their quality of life improves vastly within just one month of the transplant," said Rondelli, who is also the Michael Reese Professor of Hematology in the UIC College of Medicine. "They are able to go back to school, go back to work, and can experience life without pain."
Sickle cell disease is inherited. It primarily affects people of African descent, including about one in every 500 African Americans born in the U.S. The defect causes the oxygen-carrying red blood cells to be crescent shaped, like a sickle. The misshapen cells deliver less oxygen to the body's tissues, causing severe pain and eventually stroke or organ damage.
Sickle Cell Natural Healing: A Mother's Journey
Doctors have known for some time that bone marrow transplantation from a healthy donor can cure sickle cell disease. But few adults were transplanted because high-dose chemotherapy was needed to kill off the patients' own blood-forming cells -- and their entire immune system, to prevent rejection of the transplanted cells, leaving patients open to infection.
In the new procedure, patients receive immunosuppressive drugs just before the transplant, along with a very low dose of total body irradiation -- a treatment much less harsh and with fewer potentially serious side effects than chemotherapy.
Next, donor cells from a healthy and tissue-matched sibling are transfused into the patient. Stem cells from the donor produce healthy new blood cells in the patient, eventually in sufficient quantity to eliminate symptoms. In many cases, sickle cells can no longer be detected. Patients must continue to take immunosuppressant drugs for at least a year.
In the reported trial, the researchers transplanted 13 patients, 17 to 40 years of age, with a stem cell preparation from the blood of a tissue-matched sibling. Healthy sibling donor-candidates and patients were tested for human leukocyte antigen, a set of markers found on cells in the body. Ten of these HLA markers must match between the donor and the recipient for the transplant to have the best chance of evading rejection.
In a further advance of the NIH procedure, physicians at UI Health successfully transplanted two patients with cells from siblings who matched for HLA but had a different blood type.
In all 13 patients, the transplanted cells successfully took up residence in the marrow and produced healthy red blood cells. One patient who failed to follow the post-transplant therapy regimen reverted to the original sickle cell condition.
None of the patients experienced graft-versus-host disease, a condition where immune cells originating from the donor attack the recipient's body.
One year after transplantation, the 12 successfully transplanted patients had normal hemoglobin concentrations in their blood and better cardiopulmonary function. They reported less pain and improved health and vitality.
Four of the patients were able to stop post-transplantation immunotherapy without transplant rejection or other complications.
"Adults with sickle cell disease can be cured without chemotherapy -- the main barrier that has stood in the way for them for so long," Rondelli said. "Our data provide more support that this therapy is safe and effective and prevents patients from living shortened lives, condemned to pain and progressive complications."

Story Source:
The above post is reprinted from materials provided by University of Illinois at Chicago. The original item was written by Sharon Parmet. Note: Content may be edited for style and length.

Daniella Macolino a 24 year old actress who pursues her dreams each day while living, and thriving, with thalassemia major

2016-09-16T21:44:00.001+05:30

When I was four months old, my family and I were on vacation in Vermont when my mom noticed I was turning yellow after my older brother took me out in the snow. She overlooked it, thinking I may have just been tired from all the traveling and playing outside. But the next day I was looking worse with bags under my eyes, so my parents rushed me to the hospital. The doctor ran some tests and broke the news to my parents that I have thalassemia major, also known as Cooley’s Anemia. Not only would I need a blood transfusion right away, I would also need to continue receiving transfusions every two weeks for the rest of my life in order to survive.

My mother was born and raised in France, and she came to America not speaking any English. Neither of my parents had any knowledge that they carried the thalassemia trait and had never even heard of it before my diagnosis. Since then, my parents have become my biggest advocates and made sure I grew up with an amazing support system of friends and family. My siblings, Paul, Joseph, and Victoria, understand what I go through and don’t look at me any differently.
Living with thalassemia has been difficult, especially as a teenager. I wanted to be like my friends—go out and have sleepovers—but couldn’t because I had to be home to take my Desferal injection. This nightly routine requires me to sleep with a needle pumping medication into my body to remove the deadly iron buildup caused by receiving frequent blood transfusions. I hated it, and it was very inconvenient for me. It was frustrating waking up with bruises on my legs and arms from the needle being in all night.

Beyond that, it was hard trying to fit in while feeling so different because I had an illness and had to go to the hospital frequently. I only told a few of my closest friends that I had this disorder. Now that I am older and more confident, I am very open about sharing my experience with everyone. This illness isn’t going to define who I am, but it will make me stronger and I know that’s why people are inspired by my story!

Isabella's Journey: Her Battle with the Blood Disorder, Thalassemia Major.

The Cooley’s Anemia Foundation has been so amazing to me and my family. I can contact the Foundation anytime I have questions or need anything and they are there for me. The amount of gratitude I have for them, I can’t even put into words! I have been able to meet the most amazing people by attending Foundation conferences and other events. We are a true community, supporting each other’s passions, goals, and dreams.
It is so important to get involved with and support the Foundation, especially if you or someone you know has thalassemia. I know I can speak on behalf of patients like me when I say that getting involved is worth it because we are raising public awareness of our disorder as well as funds for medical research. One day, there will be a cure and I believe it will come sooner than expected!

“Choose a job you love, and you will never have to work a day in your life.” -Confucius
I believe that no matter what, everyone should follow their dreams and
no obstacle should stand in the way of accomplishing that! Those who know me know that I am pursuing an acting career and I have been for a while now. I don’t know exactly what it is about being in front of the camera or on stage that makes me feel amazing… but I know that I could not live without acting.
I’ve had to sacrifice so many things in order to keep doing what I love, but I’m no stranger to challenges! This is what I want to do and I will never give up. All the hard work is paying off because each year, I find myself doing better and better in my acting career. From January to May of this year I played a leading role in an independent feature film called The Prey—look out for it in October! And in August, I will be in a short horror film which I am really excited about. Tonight, I appear in an episode of The Perfect Murder on the ID channel. It is so crazy to even think that I have made it this far! Even though I put myself down every now and then thinking that I should be doing more, I am still really proud of what I have accomplished so far.
My advice to other thalassemia patients is to not look at yourself any differently than anyone else. Live your life day by day. Do what you love and don’t listen to anyone who puts you down, because at the end of the day you are a strong individual capable of doing what you want!
Just always remember to be safe and take care of yourself. It is important to be compliant by doing your chelation EVERY DAY and staying on schedule with blood transfusions. If you’re tired or feeling ill, don’t put it to the side! Your health comes first no matter what.
Thalassemia is rare and I know many people have not heard about it, but it is just as dangerous as any other chronic illness. Every patient is different and there is a wide range of complications. Please help us raise awareness and if you have never gotten your blood tested, visit your doctor to see if you carry the trait.

Scientists find new way to use CRISPR gene editing to help fix sickle cell disease

2016-09-16T21:23:00.005+05:30

An international team of scientists led by researchers at St. Jude Children's Research Hospital has found a way to use CRISPR gene editing to help fix sickle cell disease and beta-thalassemia in blood cells isolated from patients. The study, which appears online today in Nature Medicine, provides proof-of-principle for a new approach to treat common blood disorders by genome editing.
"Our approach to gene editing is informed by the known benefits of hereditary persistence of fetal hemoglobin," said Mitchell J. Weiss, M.D., Ph.D., chair of the St. Jude Department of Hematology and one of the study's lead authors. "It has been known for some time that individuals with genetic mutations that persistently elevate fetal hemoglobin are resistant to the symptoms of sickle cell disease and beta-thalassemia, genetic forms of severe anemia that are common in many regions of the world. We have found a way to use CRISPR gene editing to produce similar benefits."
Fetal and adult hemoglobin are two different molecular forms of the essential oxygen-carrying molecule in red blood cells. Hemoglobins are made up of different combinations of four molecular subunits. Sickle cell disease and beta-thalassemia are caused by mutations in a gene encoding an adult-expressed subunit termed "beta." Disease becomes apparent after birth as the levels of adult hemoglobin take hold and levels of fetal hemoglobin decline. These mutations can affect the survival of red blood cells and inhibit oxygen delivery to tissues, causing impaired function of different organs with devastating consequences for patients. Fetal hemoglobin lacks beta subunits and has gamma subunits instead. Thus, beta-thalassemia or sickle cell disease–associated mutations, which impair the production or function of the beta subunit, do not cause problems with fetal hemoglobin, which can transport oxygen effectively in adults.
Experts have known for some time that inhibiting or reversing "gamma-to-beta" switching of hemoglobin subunits can raise levels of fetal hemoglobin in adults and significantly ameliorate the debilitating symptoms of beta-thalassemia or sickle cell disease.

"Our work has identified a potential DNA target for genome editing–mediated therapy and offers proof-of-principle for a possible approach to treat sickle cell and beta-thalassemia," added Weiss. "We have been able to snip that DNA target using CRISPR, remove a short segment in a "control section" of DNA that stimulates gamma-to-beta switching, and join the ends back up to produce sustained elevation of fetal hemoglobin levels in adult red blood cells." When the scientists edited the DNA of blood-forming stem cells derived from patients with sickle cell disease, they were able to activate those genes and produce red blood cells that had enough fetal hemoglobin to be healthy.
Recently, scientists have used several gene editing approaches to manipulate blood-forming stem cells for the possible treatment of sickle cell disease and beta-thalassemia, including repair of specific disease-causing mutations and other strategies to inhibit gamma-to-beta switching. All of these approaches remain untested in patients.
"Our results represent an additional approach to these existing innovative strategies and compare favorably in terms of the levels of fetal hemoglobin that are produced by our experimental system," said Weiss. Using genome editing to restore the hereditary persistence of fetal hemoglobin is an attractive possibility, because it can be achieved relatively easily using current technologies. The condition is known to be benign in people who inherit similar naturally occurring mutations.
At this stage, the scientists emphasize that it is still too early to begin clinical trials of the new gene editing approach. The researchers want to refine further the gene editing process and perform other experiments to minimize potentially harmful off-target mutations before in-human clinical trials are considered. Additionally, it will be important to compare different approaches head-to-head to determine which one is safest and most effective.

Source:

St. Jude Children's Research Hospital

Pediatric sickle cell study stopped early due to positive results

2016-01-29T10:25:00.004+05:30

Hydroxyurea shown as viable option for some children with sickle cell anemia

Source:: Medical University of South Carolina
Summary:: For some children with sickle cell disease, the drug hydroxyurea is as effective as blood transfusions to reduce blood flow speeds in the brain, a national sickle cell disease study has found. Increased blood flows are a major risk factor for stroke in these children, report investigators.; FULL STORY

Pediatric/hematologist Dr. Sherron Jackson of the Medical University of South Carolina examines a patient with sickle cell disease.

Credit: Photograph by Sarah Pack, Medical University of South Carolina

Pediatric/hematologist Dr. Sherron Jackson of the Medical University of South Carolina examines a patient with sickle cell disease.

Credit: Photograph by Sarah Pack, Medical University of South Carolina

"It was a privilege to be a part of this well-designed and executed study. Russell Ware presented the results at the ASH meeting, and 18 years ago, almost to the day, I presented the STOP study results to the same meeting," said Robert J. Adams, M.D., study principal investigator, MUSC professor of neurosciences and director of the South Carolina Stroke Center of Economic Excellence. "That study showed how effective transcranial Doppler risk stratification, followed by regular red cell transfusions in those with high risk blood flow, can be in the prevention of stroke in these children. This became known as the STOP protocol and its wide adoption has been associated with a sharp drop in ischemic strokes in children with sickle cell disease. The drawback of indefinite transfusions however, was a limitation to wider use of the STOP protocol. This study shows that some children can be moved from transfusion to medication after at least a year. The combined understanding and evidence from these two studies brings us closer to achieving the National Institutes' goal of a 'stroke free generation' in sickle cell disease."

Standard treatment for children with sickle cell disease who are at high risk of stroke consists of regular blood transfusions. Children who receive regular blood transfusions are then at risk for iron overload. Chelation, or iron-reduction, therapy is needed for those receiving transfusions. The National Institutes of Health (NIH)-supported study sought to answer whether hydroxyurea would provide the same benefit as blood transfusions, given these additional treatment impacts. Hydroxyurea is the only drug approved by the Food and Drug Administration to treat sickle cell disease. The Transcranial Doppler with Transfusions Changing to Hydroxyurea (TWiTCH) study was stopped early due to positive preliminary results in November 2014.
Researchers from 26 clinical sites supported by the NIH's National Heart, Lung, and Blood Institute (NHLBI) recruited and studied 121 children ages 4 to 16 years old and divided them into two groups: one that received transfusions and one that was transitioned from transfusions to daily doses of hydroxyurea.
"No child should ever have to face the prospect of suffering through a stroke," said Gary H. Gibbons, M.D., director of the NHLBI. "Our institute is striving to achieve a stroke-free generation of children living with sickle cell disease. Studies like this are vital for moving us toward this worthwhile goal."
Study authors indicated that the findings suggest that hydroxyurea could be effective at reducing risk of stroke for other patient populations, though this was not a primary goal of the study.

Story Source:
The above post is reprinted from materials provided by Medical University of South Carolina. Note: Materials may be edited for content and length.

How Vitamin A can Reduce Scarring in Blood Vessels

2016-01-29T08:23:00.000+05:30

While scarring is a natural part of any healing process, scar formation within our blood vessels can be deadly. A team of US researchers has developed a new biodegradable material with built-in vitamin A which has been shown to reduce scarring in blood vessels.

"When injury occurs, cells proliferate and migrate into the blood vessel, creating scar-like tissue. It can create blockages that impair blood flow," said lead researcher Guillermo Ameer from the Northwestern University.

The soft elastic material can be used to treat injured vessels or be used to make medical devices such as stents and prosthetic vascular grafts. Early tests have shown that the material can reduce cell migration - a major contributor to the scarring process - by 57%.

"In his new work, vitamin A is integrated into the material, harnessing the beneficial properties of vitamin A and allowing for its broader application in medical devices," the authors noted in a paper published in the ACS Biomaterials Science and Engineering.

This new advanced material brings together two major advantages. Its antioxidant component can reduce the oxidative stress that leads to chronic inflammation.

Vitamin A, which is released as the material degrades, can prevent or reduce scarring.

It can potentially also be used outside the body such as for wound-healing bandages for diabetic patients.

Because the new material releases vitamin A as it degrades, the potential for toxic build up is much lower.

Ameer's team can also control how quickly the material degrades - and thus releases the vitamin A - depending on how the material is produced in the laboratory.

The team now plans to explore the material's potential for additional applications. Vitamin A is already widely known for its anti-aging properties and topical antioxidants can be used to combat cell damage or improve wound healing.

Source: IANS

Encapsulated Human Islet Cells can Normalize Blood Sugar Read more: Encapsulated Human Islet Cells can Normalize Blood Sugar

2016-01-29T08:20:00.002+05:30

Scientists studying a mouse model of diabetes have implanted encapsulated insulin-producing cells derived from human stem cells and maintained long-term control of blood sugar -- without administering immunosuppressant drugs.

The results of the multi-institutional effort are published in Nature Medicine. People with type 1 diabetes have an overactive immune system that destroys the insulin-producing islet cells in the pancreas. Lacking that hormone, the body fails to convert sugars to usable energy, and glucose rises to harmful levels in the blood without daily insulin injections.

Islet cells have been successfully transplanted to treat type 1 diabetes, but those patients must take immunosuppressant drugs to keep their immune system from destroying the transplanted cells. Previous research had shown that rodent islet cells could normalize blood sugar levels in animal models without immunosuppression if the cells were encased in hydrogel capsules.

The semi-porous capsules allow insulin to escape into the blood, while preventing the host's immune system from attacking the foreign cells. Larger capsules, about 1.5 millimeters across, even seemed able to avoid the buildup of scar tissue, which can choke off the cells' supply of oxygen and nutrients. The new study, a collaboration led by scientists at the Massachusetts Institute of Technology and Boston Children's Hospital, used islet cells derived from human stem cells and capsules made of chemically-tweaked gel that are even more resistant to the build-up of scar tissue.

Dr. Jose Oberholzer, chief of transplantation surgery and director of cell and pancreas transplantation at the University of Illinois Hospital & Health Sciences System, professor of bioengineering at the University of Illinois at Chicago, and an author on the paper, tested several varieties of chemically-modified alginate hydrogel spheres -- in various sizes -- to see if any excelled at resisting scar-tissue formation.

Oberholzer and his coworkersat the University of Illinois at Chicago first tested the spheres to ensure they would allow the islet cells to function inside a host. Using a special microfluidic device developed at UIC under a grant from the National Institute of Diabetes and Digestive and Kidney Diseases, they delivered minute amounts of glucose into tiny wells containing encapsulated islet cells and measured the amount of insulin that seeped out.

They implanted spheres that showed promise into rodents and non-human primates to look for the development of scar tissue. They found (and reported in the journal Nature Biotechnology) that 1.5-millimeter spheres of triazole-thiomorphine dioxide (TMTD) alginate were best at allowing allowing insulin to escape while resisting immune response and the buildup of scar tissue. When implanted into a mouse model of diabetes, TMTD-alginate spheres containing human islet cells were able to maintain proper blood glucose control for 174 days -- decades, in terms relative to the human lifespan.

"When we stopped the experiment and took the spheres out, they were virtually free of scar tissue," Oberholzer said. "While this is a very promising step towards an eventual cure for diabetes, a lot more testing is needed to ensure that the islet cells don't de-differentiate back toward their stem-cell states or become cancerous," said Oberholzer. If the cells did become cancerous, he said, they could easily break through the spheres.

Oberholzer also cautioned that a cure for human diabetes would require scientists to develop techniques to grow large numbers of human islet cells from stem cells -- a worthy goal. "In the United States, there are 30 million cases of type 2 diabetes and about 2 million patients with type 1 diabetes who could potentially benefit from such a procedure," he said. "But we need to grow billions of islet cells."

Source: Eurekalert

Three Simple Suggestions for a Healthy Diet

2016-01-28T16:20:00.001+05:30

In the article below, Ellen Fung, PhD, RD of UCSF Benioff Children’s Hospital Oakland and Farah Sultan, RD of McMaster University, share some nutritional information for people with thalassemia.

One of the most common questions we are asked as nutritionists is, “What should I be eating?” In many ways, the diet for individuals with thalassemia is no different than for anyone else: the key is balance. However, the needs for certain nutrients are much higher in thalassemia. Therefore, nutrient density is very important! This means every calorie must count. Rather than worrying about which specific foods are “good” for you or which foods are “bad,” it’s better to focus on choosing a variety of foods that are packed with vitamins, minerals, fiber and other nutrients. Making smart, balanced food choices every day can help you stay healthy.
Here are some strategies you can use:

Eating Around the Rainbow: Healthy foods we eat come in a variety of colors: kale (green), carrots (orange), beets (red), red cabbage (purple). Fruit loops don’t count here! Each food derives its color from the rich concentration of antioxidants in its skin and flesh. The variety of colors comes from a diverse range of anthocyanins (plant pigments) and antioxidants (for example, carrots and sweet potatoes are orange because of the antioxidant, beta-carotene). By eating a variety of foods of different colors throughout the day (eating around the rainbow), you will be consuming more antioxidants, substances which are important for reducing the damage that can be caused by the free iron in your body.

My Plate: Smaller Portions, More Vegetables and Fruit. If you are not familiar with the “My Plate” campaign from the USDA, you should take a look at it (see below and at www.choosemyplate.gov). This newest guideline for eating healthy is a simple set-up of a small plate which is divided into portions, roughly ¼ for protein, ¼ for grain/carbohydrates and ½ of the plate set aside for fruits & vegetables. If we ate all our meals this way, we would be consuming many more vitamins and minerals in our diet. Think about this the next time you sit down for lunch and dinner.

Eat Food, not Supplements. The best way to get all of our nutrients is through our food. Most nutrients are best absorbed when they come from our food (e.g. calcium – milk, zinc – chicken) rather than in the form of supplements. Nutrients found within foods are created in such a way to avoid competition for absorption in your body whereas the form of nutrients in some supplements may result in poor absorption. Food also contains much needed fiber as well as other substances (phytochemicals, flavonoids) that are important for your health. When healthy foods are replaced by foods with poor nutrient density (e.g. empty calories) + dietary supplements, you miss out on all of the benefits of food. Not to mention the simple joys of consuming delicious, nutritious foods! However, we must be clear…Individuals with thalassemia may require certain supplements (e.g. vitamin D) in addition to their diet; but supplementation should NOT REPLACE a healthy diet.

Making healthy choices doesn’t have to be complicated — simply begin by making one change in your daily routine, such as making sure to have one colorful vegetable every day. You may just be surprised how simple it can be, and how great you can feel.
Ellen Fung, PhD RD
Associate Research Scientist
UCSF Benioff Children’s Hospital Oakland
Oakland, CA USA
Farah Sultan, RD
Master’s Degree Student, Nutritional Science
McMaster University
Toronto, ON Canada

Educating Public on Sickle Cell Disease Risk

2014-11-28T16:38:00.002+05:30

In sub-Saharan Africa, members of the public who are carriers of the hereditary disease sickle cell disease must be educated aggressively through public health campaigns to raise awareness of the risks of parenting offspring with the disease if their partner is also a carrier.

This is according to research published in the International Journal of Medical Engineering and Informatics. There are many physical and emotional public health components of sickle cell disease, explains William Ebomoyi of the Department of Health Studies College of Health Sciences, Chicago State University, Illinois, USA. Moreover, there ethical and legal considerations surrounding the screening of newborns for this potentially lethal disease.

Sickle-cell disease (SCD), also known as sickle-cell anemia (SCA) or drepanocytosis is an inherited condition in which a child of parents both of whom are carriers of the associated hemoglobin gene who inherits both copies will produce abnormal red blood cells that are rigid and often sickle-shaped. The disorder causes both acute and chronic health problems, such as repeated infections, severe attacks of pain and potentially stroke and death. Carriers of just one copy of this particular hemoglobin gene tend to have greater resistance to the lethal parasitic disease malaria compared to people without a copy of the gene. However, around 2 percent of the population of sub-Saharan Africa is born with SCD. Moreover, incidence is rising across the globe as populations migrate.

In the age of genomics, however, Ebomoyi suggests that raising awareness of the risks of having children with SCD if both parents are carriers is important. "An aggressive health education of the public is required to maintain a shared responsibility for their courtship behaviour by alerting potential suitors of their heterozygous status," he suggests. He adds that, "Major sickle cell education programmes need to be integrated into the curriculum of elementary, secondary and tertiary academic institutions."

Successful outcome prompts early end to sickle cell anemia clinical trial

2014-11-28T16:35:00.000+05:30

Conclusive data show that hydroxyurea therapy offers safe and effective disease management of sickle cell anemia (SCA) and reduces the risk of stroke, prompting early termination by the National Heart Lung and Blood Institute (NHLBI) of a key clinical trial studying the drug's efficacy.

NHLBI officials issued the announcement today, about one year before the study was originally scheduled to end. Going by the title TWiTCH (TCD With Transfusions Changing to Hydroxyurea), the Phase III randomized clinical trial at 25 medical centers in the U.S. and Canada compared standard therapy (monthly erythrocyte transfusions) with the alternative (daily hydroxyurea) for children with elevated transcranial Doppler (TCD) velocities and high risk of stroke.

"Early results indicate that TWiTCH is a success. Hydroxyurea works as well as blood transfusions to lower TCD velocities, which lowers the risk of the child having a stroke," said Russell E. Ware, MD, PhD, principal investigator of the study and director of Hematology at Cincinnati Children's Hospital Medical Center, which served as the study's Medical Coordinating Center.

"A group of outside experts has been reviewing the TWiTCH data every few months to ensure the safety of children in the clinical trial and to monitor the data," Ware explained. "This group met recently and after careful consideration of the interim data results, recommended that the study be stopped since hydroxyurea worked as well as transfusions to lower TCD velocities." The NHLBI and National Institutes of Health (NIH) agreed with the recommendation.

"No child should ever suffer a stroke, which is why it was so important for the NHLBI to support the TWiTCH trial," said Gary Gibbons, MD, director of the NHLBI. "This critical research finding opens the door to more treatment options for clinicians trying to prevent strokes in children living with the sickle cell disease."

The study enrolled its first patient in September 2011 and included children between ages 4 and 16 years with sickle cell anemia and abnormally elevated TCD velocities, which increases their risk of developing a stroke. The current standard therapy for children with elevated TCD velocities is monthly blood transfusions. A total of 121 children were randomized: half received the standard therapy of transfusions while the other half received the alternate treatment with daily hydroxyurea, which has not yet been approved for children with sickle cell anemia.

The clinical data-collection portion of the study was originally scheduled for 24 months, but collection is now being stopped early, after only half of the children have completed the treatment phase.

"We did not know if hydroxyurea would reduce the risk of stroke as well as transfusions, so TWiTCH was an important research study," said Barry R. Davis, MD, PhD, principal investigator for the Data Coordinating Center at the University of Texas Health Science Center at Houston (UTHealth) School of Public Health. "The study has now shown that hydroxyurea has a similar benefit as transfusions, so the study is closing early since the main research question has been answered."

An important reason for testing hydroxyurea is that the current standard therapy of monthly blood transfusions to reduce stroke risk can lead to problems such as antibody formation and iron overload, which are increasingly recognized as a source of morbidity in young patients with SCA.
Over the past decade, the laboratory and clinical efficacy of hydroxyurea has been demonstrated in children and adults with SCA. Originally developed as a drug to treat cancer and infections, hydroxyurea boosts fetal hemoglobin production in SCA, which prevents the red blood cells from acquiring the sickled shape that fuels the many complications. Hydroxyurea has been previously shown to have clinical efficacy for a variety of sickle-related complications, but TWiTCH is the first Phase III trial that demonstrates its benefits for children with cerebrovascular disease and increased stroke risk.

Sickle Cell Anemia Treatment So Successful in Kids That Trial Is Halted

2014-11-28T16:32:00.001+05:30

Hydroxyurea pills worked as well as transfusions in reducing stroke risk, researchers report

(HealthDay News) -- A clinical trial of hydroxyurea therapy for children with sickle cell anemia has been halted a year early because the results show it is a safe and effective way to manage the disease and reduce the risk of stroke.
The announcement about the research, which was conducted at 25 medical centers in the United States and Canada, was made this week by the U.S. National Heart, Lung, and Blood Institute (NHLBI).
Researchers compared monthly blood transfusions with daily hydroxyurea pills among children with sickle cell anemia who were at high risk of stroke. To determine this, they measured the velocity of blood flow to the brain in these young patients.
With sickle cell anemia, red blood cells become stiff and sickle-shaped, blocking blood flow throughout the body. Hydroxyurea was first developed as a cancer drug, but with sickle cell anemia it reduces the number of these abnormally shaped red blood cells, the researchers said.
Early results showed that hydroxyurea "works as well as blood transfusions which lowers the risk of the child having a stroke," principal investigator Dr. Russell Ware, director of hematology at Cincinnati Children's Hospital Medical Center, said in a center news release.
"This critical research finding opens the door to more treatment options for clinicians trying to prevent strokes in children living with the sickle cell disease," NHLBI Director Dr. Gary Gibbons said in the news release.
The study began in September 2011 and enrolled 121 children, aged 4 to 16, with sickle cell anemia who showed an increased risk of stroke.
SOURCE: Cincinnati Children's Hospital Medical Center, news release, Nov. 19, 2014

HealthDay

TIF Launches “ThaliMe” App for Thalassemia Patients

2014-11-28T16:10:00.002+05:30

The Thalassemia International Federation (TIF) is taking on a new project to develop and deploy an innovative mobile program to greatly aid and improve the lives of people living with thalassemia. The envisioned program, delivered via mobile app, has the potential to reach millions of people around the world living with this challenging disease. (A video demonstration is available by clicking here.)

The overall goals of this program are to give people living with thalassemia, their families and caregivers, a private mobile support network and a suite of tools to simplify daily management and inspire overall health. The ThaliMe app helps to connect the thalassemia community to one another and to those that care for them. The application will be designed with active input from the thalassemia community to ensure value, ease of use and applicability.

ThaliMe App will be easy to use, personalized and provide users with helpful tools to manage everything from medication reminders to appointment scheduling, from mood and mobility levels, to transfusion dates and accessing the latest research. TIF views this approach to patient care and the use of mobile technology for patient empowerment and outreach as a critical component of the overall thalassemia care ecosystem.

More specifically, the goals for the program are to develop a cross-platform mobile tool that enables:
• Private, peer to peer and peer to caregiver support networks to reduce isolation and improve patients sense of support;
• Easy to use, simple health tracking and information management functionality that eases the daily challenges of disease management;
• Data visualization tools that translate health tracking into visual format thus providing an easy and motivating way to chart personal health;
• Medication and appointment reminders to encourage adherence and timely care;
• Educational and research information channel that users can post to privately or share to their social networks, more broadly, like Facebook, Twitter etc. to improve awareness, empowerment and prevention.
The App can be downloaded from the Apple store or Google Play. For more information, contact TIF at thalassaemia@cytanet.com.cy.

Correcting the genetic error in sickle-cell disease might be as simple as amending text.

2014-11-20T14:03:00.000+05:30

After some tragic early setbacks techniques that allow precise genetic manipulation have created a surge of research.

Tiny changes in DNA can have huge consequences. For years, scientists have been trying to 'fix' these mutations in the hope of treating and potentially curing some of humanity's most devastating genetic diseases. After some tragic early setbacks , techniques that allow precise genetic manipulation have created a surge of research.

DNA sequences showing the sickle-cell disease mutation (marked with an asterisk, top) and the sequence corrected (below) using gene-editing technology.

Although most existing treatments for genetic diseases typically only target symptoms, genetic manipulation or 'gene therapy' goes after the cause itself. The approach involves either inserting a functional gene into DNA or editing a faulty one that is already there, so the conditions most likely to prove curable are those caused by a single mutation. Sickle-cell disease is a perfect candidate: it is caused by a change in just one amino acid at a specific site in the β-globin gene. This results in the production of abnormal haemoglobin proteins that cause the red blood cells that house them to twist and become sickle shaped. The distorted cells get sticky, adhere to each other and block blood vessels, preventing oxygenated blood from flowing through.

Gene therapy has been used successfully in a handful of patients with immune disorders, and sickle-cell disease is among researchers' next targets. The most advanced of these projects is slated to begin clinical trials by the end of the year, and other trials are set to follow. The approaches being developed to treat sickle-cell disease take one of two forms. Conventional gene therapy, also known as gene addition, typically involves inserting new genes. Usually, a harmless virus is modified with the gene to be inserted, and this 'viral vector' is mixed with cells from the patient in vitro. The virus searches out the cells and inserts the gene into the cells' DNA, after which the cells are transplanted into the patient. Conversely, gene editing is more nuanced: in a molecular cut-and-paste, researchers cut out the faulty DNA sequence and then insert a piece of laboratory-created DNA. In both approaches, the modified DNA dictates the formation of a normal, working protein.
In sickle-cell disease, the only cells that need their DNA edited are blood stem cells — also known as haematopoietic stem cells — which are found in bone marrow. These cells continually form new red blood cells to replace those that are lost, and reprogramming just a small fraction of them will create enough perfectly formed red blood cells to eliminate disease symptoms. “Achieving genome editing via direct repair of blood stem cells represents a high hurdle,” says George Daley, director of the Stem Cell Transplantation Program at Boston Children's Hospital in Massachusetts, “but perhaps not an impossible one.”

Although these approaches are promising, several important issues must be addressed before they can be used to treat patients, such as ensuring that the therapies accurately hit their targets and do not cause irreparable harm to the cells or introduce additional genetic information that could cause problems such as cancer.

Injecting genes

Gene addition is poised to become the first sickle-cell gene therapy to be tested in humans. At the regenerative medicine and stem cell research centre of the University of California, Los Angeles, molecular geneticist and physician Donald Kohn is developing protocols for a clinical trial of this technique that is due to start enrolling patients by the end of 2014. Doctors will first harvest bone marrow from the hip bones of patients with sickle-cell disease and then extract haematopoietic stem cells from the marrow. Using a viral vector, they will insert a new, working haemoglobin gene into the cells' DNA; the old, faulty haemoglobin gene will still be present, but it will go silent as the new gene takes over. The modified cells will then be infused back into the patient's bloodstream and will migrate to the bone marrow, where they can provide a continual source of healthy red blood cells.
Kohn says that this approach has the potential to cure sickle-cell disease, and with significantly fewer side effects than a bone marrow transplant — currently the only cure (see page S14). He has tested the technique by injecting modified human haematopoietic stem cells into mice, and found that they were free of sickle cells 2 to 3 months later¹. The limiting factor in mice, Kohn says, is that they can only sustain human grafts for that long. In humans, he thinks the correction should last a lifetime — as long as 50 to 70 years.

One of the challenges in treating sickle-cell disease with gene therapy is that it is necessary to extract bone marrow to retrieve haematopoietic stem cells. With most other diseases, patients can be given drugs that entice these cells to leave the marrow and enter the bloodstream, where they can be easily harvested. But in patients with sickle-cell disease, these drugs can trigger sickle-cell crisis, an acutely painful episode during which the damaged cells stick together and block blood vessels; the crisis can be accompanied by anaemia, chest pain, difficulty breathing, blood trapped in the spleen and liver, even stroke. So researchers must harvest the bone marrow itself, which can be difficult and slow, and limits the number of cells that can be collected at one time. Kohn says that they still do not know whether this approach will yield enough haematopoietic stem cells for reprogramming. And, like other bone marrow transplant procedures, the patient still needs to undergo chemotherapy to kill off the remaining bone-marrow cells to help the genetically altered ones survive once they are reintroduced into the body.

Talented fingers

Further away from clinical trials, but potentially a lot more exciting, is gene editing. The concept was introduced in the 1990s, when artificial DNA-cutting enzymes known as zinc finger nucleases (ZFNs) were first engineered. ZFNs bind to a specific section of DNA and create a break at both ends (see 'Molecular cut-and-paste'). Cells will start to repair the break, at which point a specific sequence of laboratory-made DNA can be slotted into the gap. After the DNA is repaired, the cells start to create healthy copies of the gene.

In parallel to his work on gene addition, Kohn is exploring the use of ZFNs to edit sickle-cell genes. In collaboration with the firm Sangamo BioSciences in Richmond, California, he has shown that around 7% of haematopoietic cells can be repaired in culture using this technique, using a viral vector to get the ZFNs into the cells. Because the repaired cells continue to replicate, this small proportion could be enough to eventually produce a sufficient amount of working red blood cells. Kohn says that patients have shown major improvements when just 10–20% of their donor cells successfully engrafted and started to make new, healthy cells.

The advantage of gene editing over gene addition (a less complex approach) is that it provides an actual fix rather than a work around. But ZFNs are expensive and difficult to program. In 2010, a gene-editing protein called TALEN (transcription activator-like effector nuclease) was developed, which uses a similar mechanism as ZFNs but is cheaper and easier to work with. It was quickly adopted for use in sickle-cell disease.

At the Salk Institute for Biological Studies, in La Jolla, California, stem-cell biologist Juan Carlos Izpisua Belmonte uses TALENs in concert with viral vectors called HDAdVs (helper-dependent adenoviral vectors) to correct the sickle-cell mutation. Instead of harvesting haematopoietic stem cells from bone marrow, Izpisua Belmonte's team takes easily harvestable cells, such as blood, skin or fat cells, and then turns them into induced pluripotent stem (iPS) cells, which can be converted into any cell type. The researchers correct the haemoglobin gene defect in vitro using gene editing, then differentiate the repaired iPS cells into blood stem cells. From there, the researchers have a couple of choices. The repaired cells could simply be infused into a patient's bloodstream, where they would make their way into the bone marrow and start to make healthy haematopoietic cells.

But Izpisua Belmonte is also working on a cure that could work inside the bone marrow itself. His team is combining TALENs with a different viral vector, HDAdVs, to boost the success rate of gene editing, and the researchers are working on a plan to administer their hybrid vector directly into the bone marrow, so the genetic fix would take place inside the patient's body. Although each infusion into the marrow might correct only 1% of the cells, ten such procedures over the course of several months — something Izpisua Belmonte and his research associate Mo Li think is feasible in terms of time and cost — could alleviate the symptoms of sickle-cell disease. “Little by little, you are correcting the disease in vivo,” says Izpisua Belmonte. So far, this 'hybrid vector' technique has shown promising efficacy in umbilical-cord blood stem cells.

Sickle-cell disease results when both copies of the haemoglobin gene are faulty, and fixing just one of the genes is sufficient to make a big health improvement. As Li points out, people who carry one copy of the mutated gene, a genetic condition referred to as 'sickle-cell trait', do not show symptoms. “In fact, many of the world's best sprinters have the sickle-cell trait, he says. “Our approaches will most likely restore one mutated copy to its wild-type sequence, leaving the other copy untouched.”
CRISPRs (clustered regularly interspaced short palindromic repeats) are the most recent addition to the gene-editing toolbox. Whereas ZFNs and TALENs use a protein to lock on to a specific section of DNA, CRISPRs use a 'guide RNA'. These guide RNAs are much easier to program than the proteins in TALENs and ZFNs, as well as being cheaper and more efficient. CRISPRs also make it possible to perform multiple genetic manipulations in one go. CRISPRs work in combination with the Cas9 (CRISPR-associated 9) nuclease: after the CRISPR locks on to the target gene, Cas9 snips both strands of the DNA, disabling the gene. The approach is less than two years old, yet many researchers are now working with CRISPRs in parallel with other in vitro techniques.

Chris Calleri/Georgia Institute of Technology

A researcher corrects a mutation in the β-globin gene that causes sickle-cell disease.

There are safety hurdles to be overcome before gene editing is used in humans, especially because it involves a permanent change in the genome. The thorniest issue is 'off-target activity' — unintended changes to the genome away from the target gene.

Gang Bao, a biomedical engineer at the Georgia Institute of Technology in Atlanta, is developing gene-editing strategies for sickle-cell disease and is paying particular attention to the challenge of limiting off-target effects. He notes that if erroneous cuts happen in a cancer-causing gene, they could potentially trigger tumour growth. Even a rate of off-target activity lower than 1% could still pose serious health risks. So that the technology can move forward, researchers need to have a better understanding of off-target effects. There are two main issues: determining exactly where the off-target cuts occur and at what rate.

Bao's group has created software to predict where the off-target effects might occur for the different gene-editing techniques. In a paper published in May, his team reported that their software predicted 114 potential off-target sites across the whole genome for the CRISPR/Cas9 system, and experiments confirmed 15 of them by sequencing the cleaved DNA².

Izpisua Belmonte's team is also looking at the rate of unwanted mutations caused by gene-editing techniques. The group created iPS cell lines and then edited half of the cells using HDAdVs and TALENs³, but left the other half unedited. The edited cells had no more mutations than the unedited ones, indicating that — in contrast to Bao's findings for CRISPRs — the use of TALENs does not seem to make cells any less safe. Although human testing is still a few years off, they say that these results give them optimism about the potential for gene editing to work.
The other major challenge for gene-therapy researchers is ensuring that the edited stem cells survive and generate healthy red blood cells after they are reinserted into the bone marrow. Edited cells often die because of the amount of stress they undergo during therapy. Researchers might be able to improve the cell-survival rate by delivering other types of cells at the same time, and the speed of gene editing also seems to be important: the longer the cells are cultured in vitro, the less likely they are to survive. “Let's see if we can perform the whole procedure in four hours instead of four days,” says Bao.

Future repair toolboxes

Based on his research so far, Bao thinks that CRISPRs are the best method for generating DNA breaks, but they are also more likely to cause off-target activity. TALENs are less efficient than CRISPRs, but they seem to have fewer off-target effects. The rate of on-target activity for CRISPRs is between 40% and 80%, whereas the on-target rate for TALENs is between 20% and 50%, Bao says. The rate of off-target activity varies depending on the type of cells and the nuclease used. “If we have a way to overcome the off-target and [cell-survival] problems, CRISPR is a very promising technology,” he says.

Kohn has compared ZFNs, TALENs and CRISPRs, and thinks all three have therapeutic potential for patients with sickle-cell disease. The techniques are all good at slicing DNA; now the remaining challenges are delivering them to the target cell and accurately repairing the gene after the break.
Ultimately, for sickle-cell gene therapy to become reality, the details must be sorted out on a large scale. Tinkering with human genes can yield both devastating and remarkable results, and the difference between the two often lies in a single nucleic acid of a single gene. This places a heavy responsibility on the shoulders of every researcher in the field, but the vast potential of gene therapy makes that burden worthwhile.

East and West African sickle cell anaemia are genetically similar

2014-11-20T13:56:00.003+05:30

African collaboration unpicks disease variations by combining local genomic research with large-scale genome-wide association techniques

Sickle cell anaemia is most common in Africa and up to 11,000 children are born with the condition every year in Tanzania alone. Yet most of what is known about the genetic basis of this inherited disease comes from studies of US-based or UK-based African-Caribbean populations.

In African-American populations genetic variations can influence the ability to produce foetal haemoglobin by as much as 50 per cent, but knowledge of this effect in East African populations is scant. A collaboration between research teams in Tanzania and the UK applied the power of the genome-wide association techniques to the genomes of 1,213 individuals in Tanzania to confirm whether or not the same variations are at work in an East African population and to identify possible new ones.

Sickle cell anaemia is painful and disabling disease caused by variations in a gene involved in producing adult haemoglobin. But people who have greater levels of the foetal form of haemoglobin in their bloodstream are less affected. This first large-scale genomic study based in Tanzania has revealed a number of regions in the genome that appear to have an effect on foetal haemoglobin levels and will guide future research into African populations.

"By carrying out a large-scale genome-wide association study we have, for the first time, been able to identify powerfully the prevalence of genetic variants involved in sickle cell anaemia in the Tanzanian population and how that compares with other populations," says Siana Nkya Mtatiro, co-first author of the paper from Muhimbili University of Health and Allied Sciences. "We have also identified suggestive additional variants, which can now be studied further by the research community in the search for interventions for sickle cell anaemia in patients in Africa and worldwide."

The research confirmed the association of genetic variations near the genes BCL11A and HBS1L-MYB with sickle cell anaemia in the Tanzanian population but found that variations in HBB, which are associated with the disease in African-American populations, are not significant in East African populations. In addition, the study hinted at additional associations that require confirmation in other populations.

The collaboration between research teams in Tanzania and the UK carried out a genome-wide association study of 1,213 individuals in Tanzania with sickle cell anaemia and confirmed that BCL11A and HBS1L-MYB are connected with the disease. [Muhimbili University of Health and Allied Sciences]

"We were unable to validate any of our new suggestive associations in a group of UK samples we used for comparison. This suggests we need bigger studies to more completely understand the genetics of this disorder," says Jeff Barrett, senior author from the Wellcome Trust Sanger Institute.
The work was a joint effort drawing on the skills and techniques developed by Tanzania- and UK-based teams and the free flow of information between them. The samples were gathered in Tanzania and genotyped at the Sanger Institute, the genome-wide scan was carried out by the UK-based team and subsequent data analysis was carried out the African-based researchers.

"This work demonstrates how scientists in Africa can collaborate both with one another and with colleagues in Europe to provide greater insight into the genomic landscape of health and disease in Africa, the cradle of humanity," says Julie Makani, senior author on the study from Muhimbili University of Health and Allied Sciences. "We hope that our approach could be used as a model for other researchers working to understand the genetic basis of health and disease in Africa."
The research was supported by the Wellcome Trust, which encourages collaborations between researchers on different continents to apply cutting-edge genomic techniques in low- to middle- income countries. Trust-funded research in this area aims to increase our understanding of diseases that might otherwise be neglected.

"This is an important contribution to sickle cell disease research, which clearly demonstrates how successful genomics research collaborations - in this case between researchers in Tanzania and the Wellcome Trust Sanger Institute - can be achieved," says Jimmy Whitworth, Head of Population Health at the Wellcome Trust. "The results of this study will form a firm foundation for further studies of the genetic basis for sickle cell disease and potential avenues for treatment in sub-Saharan Africa."

Acetate supplements speed up red blood cell production, anemia research shows

2014-11-20T13:13:00.000+05:30

Researchers seeking novel treatments for anemia found that giving acetate, the major component of household vinegar, to anemic mice stimulated the formation of new red blood cells.

UT Southwestern Medical Center researchers seeking novel treatments for anemia found that giving acetate, the major component of household vinegar, to anemic mice stimulated the formation of new red blood cells.

Currently, the hormone erythropoietin is administered to treat anemia, but this treatment carries with it side effects such as hypertension and thrombosis (blood clotting). The new research, which was performed in mice, suggests that acetate supplements could eventually be a suitable supplement or possibly even an alternative to administration of erythropoietin.

"Using rational interventions based on the mechanistic insights gleaned from our current studies, we may be able to treat acutely or chronically anemic patients with acetate supplements and thereby reduce the need for blood transfusions or erythropoietin therapy," said Dr. Joseph Garcia, Associate Professor of Internal Medicine at UT Southwestern, staff physician-scientist at the VA North Texas Health Care System, and senior author of the study, published in Nature Medicine.

Anemia is the most common blood disorder, affecting some 3.5 million people, including children and women of child-bearing age, as well as many elderly persons. It can have a significant impact on quality of life, leading to fatigue, weakness, and decreased immune function. People who are anemic produce insufficient red blood cells, which deliver oxygen to tissues throughout the body.

UT Southwestern researchers began their studies by identifying a critical pathway that controls the production of red blood cells in conditions of stress, such as low oxygen. Using genetically modified mice, researchers observed that low oxygen, a state known as hypoxia, stimulates the production of acetate.
Acetate, in turn, activates a molecular pathway that ultimately results in the production of red blood cells, or erythropoiesis, by triggering the production of the protein that stimulates this process, called erythropoietin.
"Our study shows that acetate functions as a biochemical 'flare,' linking changes in cell metabolism that occur during hypoxia with the activation of a selective stress signaling pathway," Dr. Garcia said.

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The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.

Sickle cell trait tied to kidney disease among blacks

2014-11-14T14:37:00.001+05:30

African Americans with sickle cell trait - generally thought to be benign, unlike sickle cell disease - may still be at increased risk of kidney disease, a new study suggests.

African Americans with sickle cell trait - generally thought to be benign, unlike sickle cell disease - may still be at increased risk of kidney disease, a new study suggests.

Based on data for more than 2,000 people, researchers found that about 19 percent of those with sickle cell trait had kidney disease, compared to about 14 percent of people without the trait.
The study team calculates that sickle-cell trait raises the risk of kidney disease by nearly 60 percent. They reported their results in JAMA and during a presentation at Kidney Week in Philadelphia.
“We set out to do this, because there has been some uncertainty and controversy around the health consequences of sickle cell trait, which is a genetic condition related to sickle cell disease,” said one of the study’s authors, Dr. Alexander Reiner from the Fred Hutchinson Cancer Research Center in Seattle.

Sickle-cell disease is an inherited disorder in which red blood cells contain an abnormal type of hemoglobin. The defective cells frequently take on a sickle- or crescent-shape and can block small blood vessels, which can lead to tissue damage or even stroke.

People with sickle cell disease have inherited two defective genes, one from each parent, whereas those with sickle cell trait inherit only one problematic gene and one healthy one - which helps to offset the effect of the malfunctioning gene.

Sickle cell disease affects about one of every 500 blacks, according to the U.S. Centers for Disease Control and Prevention. Sickle cell trait affects one in 12 blacks.

“Even though sickle cell trait has been considered to be relatively benign, it has been known that kidney complications, such as having blood in the urine, was more common in people with sickle cell trait versus people without sickle cell trait,” said the study’s lead author, Dr. Rakhi Naik from Johns Hopkins University in Baltimore.

Naik told Reuters Health that the red blood cells of people with sickle cell trait would look completely normal under a microscope.

“The theory is that under very highly stressful situations (such as a low oxygen levels) . . . there may be some localized sickling that happens in the kidney that is leading to functional impairment,” she said.

For the new study, the researchers combined data from five large U.S. studies that included 15,975 self-identified African Americans - 1,248 of them with sickle cell trait - who were followed for 12 to 26 years.

At the outset, people with sickle cell trait were 57 percent more likely overall to have chronic kidney disease than people without a defective gene. People who didn't have kidney disease at the start were 80 percent more likely to develop it if they had the sickle trait.
Kidney disease tended to appear later in life among those with sickle cell trait than it tends to do in sickle cell disease, Naik noted.

The findings were similar in each of the studies included in the analysis. Researchers accounted for other genetic factors that are tied to chronic kidney disease among African Americans and found that they did not explain the link.

The new study concludes, however, that together, other genetic factors, socioeconomic factors and sickle cell trait may explain the overall increased risk of kidney disease seen among African Americans, Reiner said.

“Exactly how much of the increased burden of kidney disease sickle cell trait explains or is explained by other factors is still an open question that will require additional study,” he said.
Testing for sickle cell disease is common in the U.S., Naik said. “As a byproduct, people with sickle cell trait are identified,” she added.

Without additional research, it’s difficult to say whether people with sickle cell trait should be screened for kidney disease, Naik said.

“They may want closer monitoring of kidney function if someone has been identified to be a sickle cell trait carrier,” Reiner said. He added that there is no specific treatment or intervention to prevent kidney failure or further decline in kidney function.

He said these findings may lead to greater awareness of the potential health impact of sickle cell trait.
“It’s a reasonably common condition in the Africa American community,” Reiner said. “It may be important in terms of greater community awareness and education, which may be important for general health.”

Additionally, he said, the findings may spur future research into how sickle cell trait might affect other systems in the body.
SOURCE: bit.ly/1EzO9tS JAMA, online November 13, 2014.

Anemia: One-minute point-of-care test shows promise in new study

2014-11-10T16:20:00.000+05:30

A simple point-of-care testing device for anemia could provide more rapid diagnosis of the common blood disorder and allow inexpensive at-home self-monitoring of persons with chronic forms of the disease.

A simple point-of-care testing device for anemia could provide more rapid diagnosis of the common blood disorder and allow inexpensive at-home self-monitoring of persons with chronic forms of the disease.

Erika Tyburski is shown with a prototype device for point-of-care testing of anemia. The device could enable more rapid diagnosis of the common blood disorder and allow inexpensive at-home self-monitoring of persons with chronic forms of the disease.

The disposable self-testing device analyzes a single droplet of blood using a chemical reagent that produces visible color changes corresponding to different levels of anemia. The basic test produces results in about 60 seconds and requires no electrical power. A companion smartphone application can automatically correlate the visual results to specific blood hemoglobin levels.

By allowing rapid diagnosis and more convenient monitoring of patients with chronic anemia, the device could help patients receive treatment before the disease becomes severe, potentially heading off emergency room visits and hospitalizations. Anemia, which affects two billion people worldwide, is now diagnosed and monitored using blood tests done with costly test equipment maintained in hospitals, clinics or commercial laboratories.

Because of its simplicity and ability to deliver results without electricity, the device could also be used in resource-poor nations.
A paper describing the device and comparing its sensitivity to gold-standard anemia testing was published August 30 in The Journal of Clinical Investigation. Development of the test has been supported by the FDA-funded Atlantic Pediatric Device Consortium, the Georgia Research Alliance, Children's Healthcare of Atlanta, the Georgia Center of Innovation for Manufacturing and the Global Center for Medical Innovation.

"Our goal is to get this device into patients' hands so they can diagnose and monitor anemia themselves," said Dr. Wilbur Lam, senior author of the paper and a physician in the Aflac Cancer and Blood Disorders Center at Children's Healthcare of Atlanta and the Department of Pediatrics at the Emory University School of Medicine. "Patients could use this device in a way that's very similar to how diabetics use glucose-monitoring devices, but this will be even simpler because this is a visual-based test that doesn't require an additional electrical device to analyze the results."
The test device was developed in a collaboration of Emory University, Children's Healthcare of Atlanta and the Georgia Institute of Technology -- all based in Atlanta. It grew out of a 2011 undergraduate senior design project in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory University. In 2013, it was among the winners of Georgia Tech's InVenture Prize, an innovation competition for undergraduate students, and won first place in the Ideas to SERVE Competition in Georgia Tech's Scheller College of Business.

Using a two-piece prototype device, the test works this way: A patient sticks a finger with a lance similar to those used by diabetics to produce a droplet of blood. The device's cap, a small vial, is then touched to the droplet, drawing in a precise amount of blood using capillary action. The cap containing the blood sample is then placed onto the body of the clear plastic test kit, which contains the chemical reagent. After the cap is closed, the device is briefly shaken to mix the blood and reagent.

"When the capillary is filled, we have a very precise volume of blood, about five microliters, which is less than a droplet -- much less than what is required by other anemia tests," explained Erika Tyburski, the paper's first author and leader of the undergraduate team that developed the device.
Blood hemoglobin then serves as a catalyst for a reduction-oxidation reaction that takes place in the device. After about 45 seconds, the reaction is complete and the patient sees a color ranging from green-blue to red, indicating the degree of anemia.

A label on the device helps with interpretation of the color, or the device could be photographed with a smartphone running an application written by Georgia Tech undergraduate student Alex Weiss and graduate student William Stoy. The app automatically correlates the color to a specific hemoglobin level, and could one day be used to report the data to a physician.

To evaluate sensitivity and specificity of the device, Tyburski studied blood taken from 238 patients, some of them children at Children's Healthcare of Atlanta and the others adults at Emory University's Winship Cancer Institute. Each blood sample was tested four times using the device, and the results were compared to reports provided by conventional hematology analyzers.

The work showed that the results of the one-minute test were consistent with those of the conventional analysis. The smartphone app produced the best results for measuring severe anemia.
"The test doesn't require a skilled technician or a draw of venous blood and you see the results immediately," said Lam, who is also an assistant professor in the Coulter Department of Biomedical Engineering. "We think this is an empowering system, both for the general public and for our patients."

Tyburski and Lam have teamed up with two other partners and worked with Emory's Office of Technology Transfer to launch a startup company, Sanguina, to commercialize the test, which will be known as AnemoCheck™. The test ultimately will require approval from the FDA. The team also plans to study how the test may be applied to specific diseases, such as sickle cell anemia -- which is common in Georgia.

The device could be on pharmacy shelves sometime in 2016, where it might help people like Tyburski, who has suffered mild anemia most of her life. "If I'd had this when I was kid, I could have avoided some trips to the emergency room when I passed out in gym class," she said.
About a third of the population is at risk for anemia, which can cause neurocognitive deficits in children, organ failure and less serious effects such as chronic fatigue. Women, children, the elderly and those with chronic conditions such as kidney disease are more likely to suffer from anemia.

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The above story is based on materials provided by Georgia Institute of Technology. The original article was written by John Toon. Note: Materials may be edited for content and length.