Beginning with genes that are disrupted in patients with neurodegenerative disease, Dr. Taylor’s lab team first determines the normal function of those genes and then looks at how their mutation causes disease, taking advantage of any model or experimental system that gets the researcher closer to an answer.

This strategy has led Dr. Taylor to discover that some neurodegenerative diseases, including amyotrophic lateral sclerosis and frontotemporal dementia, are caused by defects in the assembly, disassembly or clearance of cellular packages of RNA and protein known as RNA granules. He has shown that these types of defects in RNA metabolism can also cause degenerative muscle diseases.

Dr. Taylor’s team is now investigating the role of RNA granules in regulating gene activity and exploring how the granules are assembled.

We look forward to welcoming Dr. Taylor, the 17th winner of the Jacob’s Ladder Norman Saunders Award, to Toronto and to the Hospital for Sick Children’s Grand Rounds in the spring of 2020.

We look forward to welcoming Dr. Brais in Toronto to receive his award on October 7^th, 2020.  He will also present a speech, albeit virtually, to Paediatrics Grand Rounds at The Hospital for Sick Children on that same date.

In late 1997, the wonderful people at our local Starbucks came to us, telling us, that they were going to do a fundraiser in support of the Gene Replacement Therapy trial that Jacob was going to participate in at Yale. And from that point, Jacob’s Ladder was born. Well, almost, kick in the support and guidance of our family and Bert Stitt, then The Canadian Foundation for Control of Neurodegenerative Disease, dba Jacob’s Ladder was born. Community.

The focus of the charity was to support some very directed objectives, and for that we needed to raise funds. As with the support of Starbucks, we reached out to our community, which at the time was primarily, young families, their parents and grandparents and the companies they worked for and supported. Everyone helped.

Operating on a shoestring, as we continue to do, we enlisted volunteers to run the organization in any way we could. I can remember vividly ‘receipt writing nights’, with 10+ people gathered around a dining room table handwriting donation receipts, stuffing envelopes and mailing them. That continued for many years until it became too onerous to service the needs of our ever growing donor base. Shortly thereafter, we automated with a proprietary software program (still in use today) developed by Dan Litvack, a volunteer. That automation, under the watchful eye of Bert Stitt and our volunteer auditor to this day, Harvey Taraday, helped us take the next step as a charity. We are forever thankful for their commitment and continued support.

That’s how we started, and to be honest, that’s how we grew. Community.

Along with all the growth, we still needed support, but this time we needed a real pro. Ellen, myself and our board could only do so much-so it was that fateful day, Nora Glass, a neighbour, came into our lives. Remember, ‘and this too shall change’, and wow, when Nora came along, did things change! She is, and always has been, that warm caring voice behind every phone call, every receipt and every newsletter over the years. Thank you Nora.

In all this time, the underlying premise behind Jacob’s Ladder continued; supporting incredible projects, accomplishing major milestones, with the community behind us all the way. That has never changed.

In fact, that community support and involvement is what drove us (Ellen and team) to develop more community centric events, like the Family Fun Days, The Jake’s Gigantic Gives, and more recently Rock with Jake and Jake’s Jams. These were designed with our community in mind, as they grew and their interests changed, we had to do the same.

Jacob’s lessons to us as a family, to our community were at the core of everything we did. And that was felt in every event, every newsletter and every communication we delivered.

Jacob’s Ladder developed into a conduit for Jacob’s voice and everyone was listening. We all strived to be kinder, more present and appreciative in today’s distracting world.

From Jacob’s Ladder, spawned Project Give Back, another values based organization run by Ellen and team, promoting strong community development in our future leaders within the school system. Spreading these messages and ideals through our young people has had a global impact as these new influencers develop a voice of their own on the world stage.

While Jacob’s Ladder, The Canadian Foundation for Control of Neurodegenerative Disease will cease operations on December 31 2019, almost 22 years after it’s inception, our values, our accomplishments, and our foundation will continue to be strong for generations to come.

To our board, to our donors, and most of all, to our entire community; your support, your guidance and most of all, your love has helped us communicate Jacob’s message throughout all these years. Thank you, and please don’t stop sharing these messages.

Thank you for helping us climb to a cure.

Jeff and Ellen.

My final note – know that if Ellen shows up at your door, things are going to happen.

Nora Glass
Executive Director

When we were warmly welcomed into Jacob’s Ladder in 2005, our goal was to fund research to find a cure for Pelizaeus-Merzbacher Disease (PMD). Over the years, we provided funding for several projects that furthered our goal. Unfortunately, a cure is still a dream for PMD families and we are hopeful that one day a treatment can be found.

Over the course of Jacob’s almost 18 years, there are some outstanding healthcare providers who demonstrate exceptional care and thoughtfulness towards our son and our family. In times of crisis, little acts of kindness have a tremendous impact. It is for that reason that we are pleased to announce the establishment of an endowment fund at Holland Bloorview Kids Rehabilitation Hospital named for Jacob Trossman: Jake’s Award for Extraordinary Healthcare Providers.

Jeff and Ellen taught Andrew and me that having a Jacob with a neurodegenerative disease does not mean a life of seclusion and sorrow. Through their example, we are able to give our Jake a life filled with fun, laughter and lots of love.

 And through your generous donations, we will be able to reward people who help families like ours in meaningful ways.

If you would like more information, please contact me at marcy.white@rogers.com or 416-420-9392.

Personally, I am deeply grateful for the two years of funding from Jacob’s Ladder to investigate the little-known gene called PLA2G6 that lies
behind three related neurodegenerative diseases, each one fatal and without treatment or cure.
Your gift allowed my lab to use our expertise in Drosophila (fruit fly) modelling to learn more about this poorly understood gene and its impact on neurodegeneration, with the long-term goal of identifying targets that could lead to therapies for infantile neuroaxonal dystrophy (INAD), atypical neuroaxonal dystrophy (aNAD), and Dystonia- Parkinsonism (DP).

GENERATING A DISEASE MODEL
In Year 1 of the study, your funding allowed my team to develop a robust Drosophila model and use it to probe the effect of PLA2G6 mutations on neurodegeneration in humans. We discovered that the loss of the fruit fly’s equivalent of PLA2G6 caused deficits in motor movements, motor coordination, and psychomotor learning, the
effects were progressive, and lifespan was severely shortened—key features of neurodegeneration in humans with PLA2G6 mutations. We shared our results with the research community in an article published in February 2018 in the prestigious journal Scientific Reports, with the contribution of Jacob’s Ladder acknowledged.

MODELLING PATIENT-SPECIFIC MUTATIONS
Building on Year 1, the key activity in our second year has been to develop our Drosophila model into patient-specific models for PLA2G6 mutations. We’ve developed models for 7 patients—2 for INAD, 2 for aNAD, 2 for DP, and 1 for a never-before seen mutation in a SickKids patient, found by scientist and staff neurologist Dr. James Dowling. We know that each condition is linked to a mutation in PLA2G6, but the mutations are in different parts

of the gene—and the location and function of the mutation seem to make the difference between a child diagnosed with INAD who lives for less than a year and a child diagnosed with DP who may live into early adulthood.

Up until now, we’ve simply not had good animal models for these ultra-rare diseases of childhood neurodegeneration. Thanks to your support of this study, we’ve filled an important gap in our toolkit.
With robust patient-specific models, we’re able to start to understand the mechanisms behind these mutations—we now have the ability to
explore what’s taking place at the level of cells and molecules.

OUR VISION: INDIVIDUALIZED THERAPY
My hope is that these foundational insights will lead us to compounds for new therapies that could one day treat these devastating childhood diseases. With a biobank of patient-specific stem cells, we’re also now able to develop a drug screening platform to test compounds of potential using patient- specific neurons derived from their stem cells.
These are the first essential steps that may lead to individualized therapies in the future.

By focusing on INAD, aNAD, and DP, we hope to identify common disease pathways or shared underlying defects and possible
therapies that could benefit people living with neurodegeneration across the lifespan, from early infancy to old age. Thank you for helping advance knowledge that we hope will transform lives in the future.

Sincerely yours,

Dr. Gabrielle Boulianne Senior Scientist
Developmental & Stem Cell Biology

https://www.dropbox.com/sh/nqve06kvs5w0k97/AAByXtH3gSs4DtaZcUpDHmq0a?dl=0

Individual Performance links:

Abby & Sarah Ginsberg https://www.dropbox.com/s/y12wxbz9md0ozf0/Abby%20%26%20Sarah%20Ginsberg.mp4?dl=0

Aja Neinstein, Paige Smith, & Taylor Florence

https://www.dropbox.com/s/tcl6ehl4a5u9wod/Aja%20Neinstein%2C%20Paige%20Smith%2C%20%26%20Taylor%20Florence.mp4?dl=0

Amy Sky & Ezra Jordan https://www.dropbox.com/s/qqt1zpt2yq7is9f/Amy%20Sky%20%26%20Ezra%20Jordan.mp4?dl=0

Aviva & Don https://www.dropbox.com/s/8ikiofyph9bjdko/Aviva%20%26%20Don.mp4?dl=0

Caroline Brooks & Robbie Roth https://www.dropbox.com/s/1ap2em0gdxapjzf/Caroline%20Brooks%20%26%20Robbie%20Roth.mp4?dl=0

Cole, Halle, & Ethan https://www.dropbox.com/s/5owhc93eva7pekz/Cole%2C%20Halle%2C%20%26%20Ethan.mp4?dl=0

CZN https://www.dropbox.com/s/uu8pa3u1s5nhx0i/CZN.mp4?dl=0

Hayden Desser https://www.dropbox.com/s/7ibquwgebexhx1s/Hayden%20Desser.mp4?dl=0

I Rise Above https://www.dropbox.com/s/5nwrruoelq7lags/I%20Rise%20Above.mp4?dl=0

Jackie Richardson https://www.dropbox.com/s/us0fqn4cpzr8iq5/Jackie%20Richardson.mp4?dl=0

Janelle, Seth, Lily, Jordy, Ethan, & Zack https://www.dropbox.com/s/rowp1o1e8ce2kog/Janelle%2C%20Seth%2C%20Lily%2C%20Jordy%2C%20Ethan%2C%20%26%20Zack.mp4?dl=0

Michelle Newman & Amanda Silcoff https://www.dropbox.com/s/k4l1n5reg0mnqd2/Michelle%20Newman%20%26%20Amanda%20Silcoff.mp4?dl=0

Naomi Blicker, Rochelle Monson, Stacy Winter, Joanna Pearl,  Amber Walton Amar https://www.dropbox.com/s/tin1soow67h7x6n/Naomi%20Blicker%2C%20Rochelle%20Monson%2C%20Stacy%20Winter%2C%20Joanna%20Pearl%2C%20%20Amber%20Walton%20Amar.mp4?dl=0

Rachel & Tyler Simmons https://www.dropbox.com/s/i2wzyrixy6v5hi2/Rachel%20%26%20Tyler%20Simmons.mp4?dl=0

Seth Zosky https://www.dropbox.com/s/2lt9k158bkfof25/Seth%20Zosky.mp4?dl=0

Stacey, Jenn, Seth, & Zack https://www.dropbox.com/s/p70x29y5pm01cjj/Stacey%2C%20Jenn%2C%20Seth%2C%20%26%20Zack.mp4?dl=0

Tyler Simmons & Jack Lenz https://www.dropbox.com/s/e37o3ldafqaau0e/Tyler%20Simmons%20%26%20Jack%20Lenz.mp4?dl=0

From the very beginning the Hospital for Sick Children joined with us to create a panel to recommend and invite the world’s best to come to Toronto to accept this award. This project was unanimously well received from the onset and to date 15 outstanding candidates have attended. We again congratulate all previous award recipients who have shown outstanding dedication in the field of genetics:

Huda Zoghbi M.D. (2000) Baylor College, Houston, Texas Evan Snyder, M.D., Ph.D. (2001) Sanford-Burnham Medical Research Institute, La Jolla, California Anthony Monaco M.D., Ph.D. (2002) University of Oxford, Oxford, England Gregory Grabowski Ph.D. (2003) Cincinnati Childrens’ Hospital, Cincinnati, Ohio Salvator DiMauro M.D. (2004) Columbia University, New York City, New York Hugo Moser M.D. (2005) John Hopkins University, Baltimore, Maryland Eric Shoubridge Ph.D. (2006) McGill University, Montreal, Quebec Charles R. Scriver CC GOQ FRSC FRS (2007) McGill University, Montreal, Quebec Stephen T. Warren Ph.D, FACMG (2008) Emory University, Atlanta, Georgia Charles Thornton Ph.D, MBA (2009) University of Maryland, Maryland Brian Robinson Ph.D. (2011) The Hospital for Sick Children, Toronto, Ontario Cornelius Jakobs Ph.D. (2013) VU Medical Centre, Amsterdam, The Netherlands Berge Minassian M.D. (2014) University of Toronto, Toronto, Ontario Adrian Bird CBE FRS, FRSE (2015) University of Edinburgh, Edinburgh, Scotland Mustafa Sahin M.D. PhD (2017) Harvard Medical School, Cambridge, Massachusetts

In March 2007 Dr. Norman Saunders, Jacob’s beloved paediatrician, passed away. To honour this incredible and incredibly important person in Jacob’s life the International Research Prize which he helped create was lovingly renamed The Jacob’s Ladder Norman Saunders International Research Prize.

On June 12th, 2019 we look forward to welcoming Fatima Bosch to speak at Grand Rounds at The Hospital for Sick Children. Fatima Bosch is a full Professor of Molecular Biology and Director of the Center of Animal Biotechnology and Gene Therapy at the Universitat Autònoma Barcelona. Professor Bosch is a Pharmacist (1980) and PhD in Biochemistry (1985) by the University of Barcelona and has conducted post-doctoral studies at Vanderbilt University (1985), Case Western Reserve University (1988-1990), and NCI-Frederick Cancer Research and Development Center (1991). She has been granted numerous awards for her accomplishments in her field during the course of her career and is also a member of the Gene Doping Expert Group of the World Anti-Doping Agency (2013-present).

Her research focuses on studying the pathophysiological causes of diabetes mellitus using transgenic animal models and developing gene therapy approaches to this disease by in vivo genetic manipulation of tissues using non-viral and viral vectors. Recently, she has applied her know-how on gene transfer technologies to the development of gene therapies for inherited metabolic disorders such as Muccopolysaccharidoses.

Dr. Sahin received his MD and PhD in neurobiology at the Yale University School of Medicine.  He completed his internship at Children’s Hospital of Philadelphia and residencies at both Children’s Hospital of Philadelphia and Boston Children’s Hospital.  He has received numerous awards, including a Mentored Clinical Scientist Development Award, a William Randolph Hearst Fund Award, a Spinal Muscular Atrophy Foundation Young Investigator Award, the 2005 Young Investigator Award from the Child Neurology Society and a 2009 John Merck Scholar Award.

Dr. Sahin’s research investigates the normal cellular functions of signaling pathways implicated in neurological disease, with an emphasis on axon growth and guidance. Further focus is on the proteins affected in tuberous sclerosis complex (TSC) and spinal muscular atrophy (SMA) – two neurological disorders whose genetic basis is well understood but whose cell biology remains unknown.  By understanding and developing new mouse models, Dr. Sahin has advanced treatments for TSC that have changed clinical practices.

As a clinical neurologist Dr. Sahin has an active practice treating patients with neurological disease.  His overall goal is “to bring new treatments to childhood neurological diseases and improve the lives of children and families affected by these conditions.”

We look forward to welcoming him in Toronto to receive his award on January 17- 18, 2018.  He will speak to Paediatrics Grand Rounds at the Hospital for Sick Children on Wednesday, followed by the award reception, and speak at Genetics Rounds on Thursday.