The multi-axis stretchable wound zipper (MSWZ) shrinks and responds like human skin to enable personalized fast and precise healing at a molecular level.

The device, outlined in Advanced Science, mechanically stretches and contracts wounds in multiple directions through a smartphone app and it was able to heal to complex wounds in rats.

The zipper supported matrix remodeling to reduce the risk of scar formation and encouraged blood flow to supply energy and nutrients for optimal healing.

Researcher Yiming Zhang, PhD, from Xinqiao Hospital in Chongqing, China, said it addressed the limitations of conventional surgical sutures or skin staples that only contract in a single direction without being able to manage the force applied.

“We believe this technology offers an innovative solution for future wound care, ultimately alleviating patient suffering and significantly accelerating the healing process,” he said.

The multi-axis wound zipper is engineered from electro-thermally driven mechanical metamaterials and is encapsulated between two layers of polyurethane dressing before use.

It is constructed from a lattice based on nickel-titanium shape-memory alloy that can freely stretch in six directions, spaced 60 degrees apart. This enables it to conform to complex wound morphologies, with precise, programmable mechanical contraction possible through the smartphone app.

A circular notch in the center of the underlying dressing allows the zipper to stick only to the wound margins and not to the center of the wound so that mechanical contraction forces do not act directly on the central wound tissue.

This “loop adhesion” design is better than traditionally uniform dressing structures, the researchers explain, as it allows the zipper to draw flat against the wound edge—like a drawstring bag—for smoother, more uniform closure.

The device also incorporates a Bluetooth-enabled microcontroller unit, which allows the patient to precisely set and dynamically regulate the wound contraction strength through a mobile app. This intelligent closure system allows contraction to be adjusted according to personal comfort and avoids the pain of over contraction.

Pre-stretched multi-axis wound zippers were better than surgical suturing for linear wounds in rats, achieving immediate and complete closure and a wound healing rate of nearly 90% on the first day.

When used for circular wounds, the wound zipper was also better than surgical suturing and had a superior wound-healing rate above 95% within eight days. It restored the epithelial barrier, reduced the width of the wound, and promoted reconstruction of the collagen matrix.

It was also able to heal the spindle- and oval-shaped wounds frequently seen in the clinic.

Maximum wound closure rates for linear, triangular, rectangular, and circular wounds were 100%, 84.85%, 81.99%, and 87.40%, respectively.

Immunohistochemistry revealed that the wound zipper promoted blood flow to deliver energy and nutrients for healing and supported matrix remodeling to reduce the formation of scar tissue.

Mechanical contraction using the device upregulated vascular regeneration-related transcription factors and speeded the restoration of local perfusion. At the same time, it promoted proliferation and migration of keratinocytes, thereby accelerating re-epithelialization.

In addition, by reducing the skin tension at the wound margin, the wound zipper inhibited the overactivation of myofibroblasts, facilitated orderly collagen matrix remodeling, and decreased the risk of scar formation.

“Collectively, these findings indicate that the MSWZ can deliver rapid, robust, and programmable multi-axis mechanical contraction suited for personalized management of diverse wound types,” the researchers concluded.

“Its conformability to skin and favorable safety profile further support its potential for future clinical translation.”

The post App-Controlled “Wound Zipper” Aids Bespoke Skin Healing appeared first on Inside Precision Medicine.

“The study shows that artificial intelligence is capable of deriving molecular information directly from routine tissue sections and thus fundamentally changing cancer diagnostics,” said lead author Darui Jin, PhD, a postdoctoral fellow at DKFZ.

CNS tumors encompass a broad range of diseases with substantial molecular and morphological diversity. DNA methylation profiling is currently the gold standard for classifying many brain tumors, but the tests require specialized labs employing expensive analytical tools and require sufficient amount of tumor material, which can be difficult to obtain in some instances. Results from these tests typically take about two weeks to return results. The reliance on molecular testing has also created barriers to diagnosis in some clinical settings.

“Faster and more widely accessible methods are therefore needed,” the researchers wrote. Existing alternatives such as nanopore sequencing also require specialized instruments and tissue preparation. Routine H&E histopathology remains the most widely available diagnostic material worldwide.

The development of Hetairos has been made possible from significant advances in computer vision and digital pathology. Prior research has established that AI algorithms can detect molecular features in tissue samples and classify tumors into molecularly defined categories. The researchers noted that previous research has shown that AI models can estimate methylation signals from standard H&E slides and predict specific molecular alterations, but “an artificial intelligence (AI)-based diagnostic solution for H&E slides that covers the entire spectrum of CNS tumors, as currently only possible with methylation testing, is still missing.”

To develop Hetairos, the team trained and validated the system using more than 11,000 digitized tissue sections from 9,606 patients treated at 11 medical centers across four continents. Diagnoses used for training were primarily established through DNA methylation diagnostics. The resulting model was designed to classify tumors into 102 molecular subtypes that span nearly the entire WHO classification spectrum for CNS tumors.

An important element of the system is it can estimate the level of confidence of its predictions.

“Crucial to Hetairos’s applicability across cohorts are its realistic confidence estimates, which help judge its prediction accuracy,” the researcher wrote. “Depending on the cohort, Hetairos made high-confidence predictions in 50–70% of cases, and those predictions were found to be the correct diagnosis in nearly 90% of instances.”

As it has become custom, the system was also tested directly against human experts. Five board-certified neuropathologists reviewed 210 cases using only tissue sections. Hetairos achieved an accuracy rate of 68%, compared with 30% for the specialists. When the three most likely diagnoses were considered, the AI tool was 84% accurate versus about 50% for the neuropathologists.

“The results show that modern AI systems are now capable of recognizing extremely subtle morphological patterns that are difficult even for experienced specialists to distinguish,” said Felix Sahm, a project leader at DKFZ.

A prospective evaluation of Hetairos in clinical practice analyzed 210 tumor samples alongside routine diagnostics without, but its results weren’t used to influence patient management. While complete molecular testing required an average of about 12 days, Hetairos generated results in approximately 12 minutes after digitized slides were available. Including slide preparation and scanning, findings could often be produced within 24 hours to two days.

This much speedier diagnosis could help clinicians initiate targeted treatments sooner and guide additional testing, but rather than replacing molecular testing, the developers envision Hetairos as a triage and decision-support tool.

“We developed Hetairos primarily as a tool to support diagnostics,” Sahm said. “It is not intended to replace molecular analyses, but rather to specifically complement and accelerate them. The technology could make an important contribution, particularly in countries or regions with limited resources, as it is based on standard tissue sections used worldwide.”

The post AI Tool Classifies 102 CNS Tumor Subtypes in Minutes appeared first on Inside Precision Medicine.

“Malaria continues to be responsible for a large global health burden, with an estimated 282 million cases and 610,000 deaths in 2024,” write the authors of the study, led by Stephan Chalon, MD, PhD, vice president of experimental medicine and clinical pharmacology at the nonprofit organization Medicines for Malaria Venture. “Fast-acting antimalarial drugs are needed to address the emergence of artemisinin resistance in Plasmodium falciparum, the major cause of severe malaria worldwide.” 

Malaria infections caused by P. falciparum are typically treated with artemisinin-based combination therapy (ACT). As part of this first-line treatment, an artemisinin-derived drug dramatically reduces the numbers of malaria parasites circulating in the blood within a few hours while a companion drug with a slower mode of action eliminates the remaining parasites. 

However, artemisinin-resistant malaria infections have been steadily increasing in Southeast Asia, and more recently in East Africa. As resistance spreads, the efficacy of first-line ACT progressively declines, driving an urgent need for fast-acting alternatives to artemisinin-based drugs. 

The clinical trial evaluated the safety and tolerability of MMV367, an oral antimalarial drug candidate under development at Medicines for Malaria Venture. The drug belongs to the pyrrolidinamide class, a novel group of fast-acting antimalarials that interfere with two enzymes that are essential for malaria parasites to synthesize long-chain fatty acids.  

As part of the study, 12 healthy volunteers were inoculated with P. falciparum and then treated with MMV367 after eight days. Results showed that doses of 20mg or above were able to quickly kill the parasites, with half of them being eliminated within 4.3 hours. The drug also proved safe in all participants, showing only mild side effects in some of them.

No evidence of emerging drug resistance against this novel drug class was found during the study. However, this will need to be confirmed in future studies with a larger patient population and longer follow-up period. While more research will be needed before this drug can reach people affected by malaria worldwide, these early clinical results support its potential as an alternative to artemisinins in antimalarial combination therapies as they increasingly lose efficacy in the face of escalating drug resistance.  

As a product development partnership (PDP), Medicines for Malaria Venture works together with major pharmaceutical companies and academic institutions to promote the development of accessible and affordable medicines to treat and prevent malaria with a major focus on addressing the needs of children and pregnant women. Since its inception in 1999, the nonprofit has delivered 19 approved medicines, with many other candidates currently at various stages of clinical development. 

The post Fast-Acting Malaria Drug Shows Promise in First-in-Human Study appeared first on Inside Precision Medicine.

“Right now, the decision to give adjuvant radiation or chemoradiation after surgery hinges almost entirely on TNM staging and surgical pathology,” explained senior author Daniel Faden, MD, director of the Head and Neck Cancer Genomics and Liquid Biopsy Program at Mass General Brigham Cancer Institute.

This means that surgeons and oncologists look at features like the number of involved lymph nodes, whether there’s extranodal extension, surgical margin status, and perineural invasion or lymphovascular invasion.

“The problem is, these are static, backward-looking variables,” Faden told Inside Precision Medicine. “They tell us what was in the tumor specimen, but they don’t tell us whether the patient has microscopic disease left behind after surgery.”

This can result in some patients receiving more treatment than they need, with potential unnecessary side effects, and others receiving less treatment than they should and later having their cancer come back.

Previous work has shown that circulating tumor (ct)HPV DNA is a promising biomarker for predicting head and neck cancer recurrence, but current assays, using droplet digital polymerase chain reaction (ddPCR), lack the sensitivity needed for detecting minimal residual disease (MRD) after surgery.

Faden and team therefore used their experience of studying HPV to build HPV-DeepSeek, a whole genome sequencing (WGS) assay that detects ctHPV DNA in blood samples.

He noted that the assay differs from most currently available MRD assays as it is not tumor-informed and does not require building a bespoke panel from each patient’s tumor. This makes HPV-DeepSeek tissue agnostic, and means the assay has a lower cost and faster turnaround times than tumor-informed WGS approaches.

Faden and team evaluated the performance of HPV-DeepSeek in the Clear-HPVca study, which included 103 patients (mean age 62 years, 89% men) with stage I to IV HPV-positive head and neck cancer who were treated with surgery.

The authors report in Science Translational Medicine that among 74 patients with ctHPV DNA status available during the postsurgery period (four days to six months after surgery, before adjuvant therapy), 23% were MRD-positive.

After a median follow-up of 27 months, patients with ctHPV DNA detected had worse outcomes than those with no ctHPV DNA. Specifically, the two-year disease-free survival rate was 60% among the patients who were MRD-positive, compared with 100% for those who were MRD-negative, and the two-year overall survival rates were 73% and 98%, respectively.

The researchers also found that HPV-DeepSeek could predict which patients benefit from adjuvant treatment; the recurrence rate was 27% among 15 MRD-positive patients who received adjuvant treatment compared with 100% among the two MRD positive patients who did not receive adjuvant treatment.

Conversely, there was no benefit of adjuvant treatment among MRD-negative patients; in this group, the recurrence rate was 3% among the 37 MRD-negative patients who received adjuvant therapy and 0% among the 21 MRD-negative patients who did not receive adjuvant therapy.

Furthermore, the assay identified molecular recurrence an average of seven months, and up to 17.5 months, earlier than clinical recurrence. With ddPCR, molecular recurrence was only detected four months earlier than clinical recurrence.

Although the team knew that HPV-DeepSeek was more sensitive than ddPCR, Faden described the size of the lead-time as striking.

“It tells us we’re detecting recurrence at a disease burden that’s genuinely clinically meaningful and actionable,” he said. “We had some patients where molecular detection preceded clinical detection by over a year. That kind of window creates real opportunities—time to discuss salvage surgery or systemic therapy before a patient ever develops symptomatic recurrence.”

Faden and team are now planning interventional trials that will investigate whether using HPV-DeepSeek to guide adjuvant therapy decisions improves outcomes and reduces toxicity.

Faden hopes that the assay will eventually be used to guide personalized treatment decisions.

“As a surgeon who treats this disease, not just a scientist who studies it, this is where I get genuinely excited—because it’s a shift in philosophy, not just methodology,” he said. “What HPV-DeepSeek does is make disease biology—specifically, whether there’s residual disease—visible in real time.”

He added: “If you can accurately detect MRD early after surgery, you can make treatment decisions based on that biology [and] the downstream implications are significant. You reduce unnecessary toxicity in patients who don’t need more treatment. You potentially intensify treatment in patients with residual disease. And you can rethink surveillance—if a patient remains MRD-negative after treatment, can we move to less frequent imaging and potentially spare them years of follow-up CT scans?”

“We’re not there yet clinically, but this is a first step—a research finding with real promise. It’s the beginning of a conversation about how to personalize care.”

The post Ultrasensitive HPV DNA Blood Test Could Help Personalize Head and Neck Cancer Treatment appeared first on Inside Precision Medicine.

The findings provide a positive snapshot that digital tools designed to address participant needs can help improve their engagement throughout the term of a clinical trail, and aid in the the collection of data that can improve the efficiency and long-term value of oncology trials.

“We were eager to offer trial participants a format to allow connection to the study team,” said Suzanne George, MD, senior author of the study project and professor of medicine at Harvard Medical School. “Nearly all participants who engaged with the tool opted in for recontact for future research which allows the ability to build a research community. PEP gives patients a direct way [to] self-report key data elements, such as specific social and economic factors which may impact a person’s cancer journey.”

The intent in developing PEP was to find new ways to improve the experience of patients enrolled in clinical trials. Digital tools have the ability to simplify access to study materials, streamline data collection, aid in remote patient monitoring, and improve communication between researchers and trial participants. Specifically, PEP was created to improve engagement, which the researchers defined as sustained and beneficial interaction between participants and researchers over the course of the study. Unlike many digital tools focused on recruitment, PEP was designed to help researchers learn directly from patient experiences and maintain communication after trial enrollment.

“Historically, there are very few, if any, instances of trials providing consistent, longitudinal communication back to the patient about the overall clinical trial,” George told Inside Precision Medicine. “The large percentage of people reporting positive experience suggests PEP’s content and delivery methods resonate with them.”

To develop PEP, The Alliance used an iterative user-centered process that included advisory board input, usability testing with 19 patients, including 12 Spanish-speaking participants, and refinement using plain-language and health-literacy principles. Rather than requiring usernames and passwords, participants received secure links by text or email that allowed direct access to portal content and surveys.

The pilot was conducted within the MCED Biobank Study, an ongoing national clinical trial investigating future blood tests for the early detection of cancer. Of the total 2,221 study people enrolled in the trial, 40% chose to use PEP. Of the 899 users, 361 completed demographic questionnaires and 310 completed surveys addressing social determinants of health.

One of the portal’s central features was bidirectional communication that included trial participants receiving study updates, newsletters, and research information. PEP users could also provide feedback and report personal information that could help researchers better understand their experiences. According to George, participant feedback has influenced both the platform’s design and future patient engagement strategies.

“As noted in our manuscript, we conducted one-on-one focused interviews with people to evaluate the PEP on all levels, from communication methods and content to data security and privacy,” she said. “Through these findings, we were able to understand the need to transcreate documents into Spanish for cultural meaning and contextual relevance, rather than just translate them word-for-word.”

Feedback also led researchers to reconsider maintaining study-specific websites.

“Participant feedback substantiated our decision to eliminate dedicated study-specific PEP website(s),” George said. “Instead, we are transitioning to an IRB-approved newsletter format delivered directly to study participants for ongoing communication and education.”

The study also showed that people using PEP were willing to provide information about social determinants of health (SDoH), such as education, insurance status, housing stability, food insecurity, and financial concerns.

“If a trial chooses to formally integrate SDoH metrics, they could be included as protocol-directed surveys done via PEP, making results directly available to the protocol investigators,” George said. “Self-reported information is critical because it allows researchers to look beyond the actual study biology.”

Collecting this kind of information can help identify barriers that may affect treatment adherence, including transportation challenges, childcare responsibilities, and financial stress.

Another notable finding was that community-based practices enrolled a higher proportion of eligible participants into PEP than academic medical centers. The reasons remain under evaluation, but George suggested that established relationships between patients and local care teams may contribute to greater acceptance of the platform.

Further, the researchers found that 98% of participants were open to health-related follow-up communications. The research team believe this is an important outcome because it creates opportunities for future re-engagement and continued participation in research activities.

While the data from the pilot showed meaningful patient engagement, there were some limitations. Participants who enrolled in PEP were more likely to be female and White than the broader study population, raising questions about whether the data would be representative across diverse populations.

“Looking forward, PEP would ideally become a standard core functionality in all oncology studies,” George noted. “However, we will need to continue to expand outreach and continue to engage the participant community, to ensure we are indeed reaching all of those who would like to be part of such a platform.”

The post Digital Portal Strengthens Patient Engagement in Cancer Clinical Trials appeared first on Inside Precision Medicine.

The researchers tested three commercially available AI-based computer-assisted detection (AI-CAD) systems on mammogram data from a large screening population. Cancer prediction scores issued by AI-CAD were elevated for a significant number of patients later diagnosed with breast cancer compared to those who remained cancer-free. The team was led by researchers at the Karolinska University Hospital in Stockholm.

“Approximately 20% of breast cancer cases demonstrate mammographic signs that are already visible to AI around six years before diagnosis,” said senior coauthor Fredrik Strand, MD, PhD, of Karolinska. “Our study confirms the potential of AI to, in some cases, find signs of cancer in the mammograms much earlier than when radiologists detected it.”

Earlier diagnosis is crucial in breast cancer, as it is for most malignancies. Although annual breast screening, using mammography, is recommended for women in the U.S. aged 40 to 74, it is known that approximately 20-25% of women show early signs of breast cancer on their scans before they are diagnosed. 

Strand’s team investigated AI’s potential to flag mammographic signs that were present up to 10 years in retrospect. The study included a total of 88,963 mammograms performed on 31,394 patients over 10 years—between January 2008 and April 2019. Of these participants, 12,072, or 38.5%, were diagnosed with cancer.

The data came from the Validation of Artificial Intelligence for Breast Imaging (VAI-B) database, which collects breast imaging data from volunteers across four regions of Sweden. The Swedish national breast screening program invites women between the ages of 40 and 74 to participate in screening examinations every two years, and each mammogram has traditionally been read by two radiologists. The average age of screening was 57.6 years.

The AI-CAD systems found many of those cancers at earlier screening points, achieving 90% specificity—distinguishing between a true positive and a true negative result—in up to 17% of patients at 10 years before diagnosis, up to 19.7% six years before diagnosis, up to 25.2% four years before diagnosis, and up to 39.3% two years before diagnosis.

“This study aims to add to the growing literature regarding the application of AI in breast cancer screening and how it can help play a role in earlier detection of breast cancer,” said Strand. “Analyzing the AI scores of screened individuals over time could provide insight into how early detectable changes arise, potentially allowing for earlier intervention.”

Breast cancer is the most commonly diagnosed cancer worldwide. It accounts for roughly 30% of all new female cancer diagnoses. In the U.S., AI-based systems have shown promise for predicting five-year risk of breast cancer and identifying women at risk of cancers that arise between regular screening mammograms. 

The post AI Detects Breast Cancer Much Earlier than Radiologists Alone appeared first on Inside Precision Medicine.

The approach, published in Cell Reports Medicine, combines two areas of cancer research that have largely advanced independently: bacterial cancer therapies and oncolytic viruses. By using tumor-targeting bacteria to protect and deliver viral genetic material, the investigators hope to overcome one of the major limitations facing systemic viral therapies for solid tumors.

“We put these two together,” said Neil Forbes, PhD, professor of chemical engineering at the University of Massachusetts Amherst and senior author of the study. “Our Salmonella protects the viral genetic material and delivers it specifically inside tumor cells.”

Combining bacterial and viral cancer therapies

Oncolytic viruses have attracted considerable attention as potential cancer therapies because they can selectively infect tumor cells, destroy them, and stimulate antitumor immune responses. However, delivering viruses to internal solid tumors has proven challenging. “If you inject the virus into the blood, it gets cleared by the immune system,” Forbes said. “You get a few to the tumor, but not enough that it either makes an effect, or you put in so many that it’s toxic.” As a result, many oncolytic virus clinical trials for solid tumors rely on direct injection into accessible tumors, limiting their use in cancers located deep within the body.

Forbes and colleagues sought to address that challenge using engineered Salmonella, which naturally accumulates within tumors after intravenous administration. The researchers modified the bacteria to invade cancer cells and then release their cargo intracellularly specifically into tumors.

Rather than administering intact viral particles, the team loaded the bacteria with plasmids containing the complete genome of an oncolytic virus. After entering tumor cells, the bacteria release the viral genetic material, which then migrates to the nucleus and begins the viral replication process.

“The Salmonella get inside the cancer cell, they release the genomic material that then traffics to the nucleus of the cancer cell, where the virus starts to work like it naturally does,” Forbes said. The virus subsequently replicates, forms infectious viral particles, destroys the host cancer cell, and spreads throughout the tumor microenvironment.

Strong responses in pancreatic and liver tumors

The researchers evaluated the platform in mouse models of pancreatic and liver cancer, using animals with fully functional immune systems. “We use mice with full immune systems because that’s the whole idea here—we’re going to trigger an immune response,” Forbes said.

The results were striking. According to Forbes, treatment produced near-complete tumor eradication in most animals. The study also demonstrated that intravenous administration was sufficient to achieve therapeutic activity. Tumor responses following systemic delivery were comparable to those observed with direct tumor injection.

“We showed that we can get the same tumor reduction from an IV injection as we do from an intratumoral injection,” Forbes said. The finding suggests that the bacterial carrier successfully protected the viral payload in circulation and delivered it to tumor sites after systemic administration.

Evidence of durable antitumor immunity

Beyond direct tumor destruction, the investigators found evidence that the therapy generated a robust adaptive immune response against cancer cells.

To test whether immune memory had developed, the researchers harvested splenocytes from treated mice and transferred them into naïve animals that had never been exposed to tumors, Salmonella, or the virus. The recipient animals were subsequently challenged with tumor cells. “In 100% of the cases they did not take any tumors,” Forbes said. “We’ve generated this antitumor immunity against the tumor.” Importantly, the protection appeared to be directed against the cancer itself rather than against the bacterial or viral components of the therapy.

According to Forbes, the findings suggest the treatment could potentially help prevent metastatic disease or tumor recurrence after elimination of the primary tumor.

Addressing safety concerns

The use of live bacteria as a cancer therapy has historically raised concerns about toxicity and safety. To address those issues, the researchers engineered additional modifications into the Salmonella strain.

During development of the platform, the team removed bacterial antiviral genes that would otherwise interfere with viral production. Unexpectedly, those modifications also appeared to improve safety. “We found that those Salmonella we made with those deletions end up being much safer,” Forbes said.

The modified bacteria were cleared more efficiently from normal tissues and were more susceptible to elimination by macrophages, reducing the likelihood of persistent infection.

While treatment was not entirely free of side effects, Forbes described the observed toxicities as relatively mild. “The side effects from any delivery of bacteria are going to be like standard flu-like symptoms,” he said. “We’re talking about late-stage cancer patients where the prognosis is usually really poor.”

Expanding the therapeutic toolbox

Although the current work remains preclinical, Forbes believes the study highlights the broader potential of engineered bacterial therapies as programmable platforms for cancer treatment. “I think that bacteria have massive potential to treat disease, specifically cancer, in ways that we can’t do with small molecules,” he said.

Unlike conventional drugs, bacteria can be engineered to carry multiple therapeutic payloads, control where treatment occurs and coordinate several biological mechanisms simultaneously.” It is very plastic, highly modifiable, very flexible,” Forbes said. “We can control timing, we can control localization, so we have a lot of power.”

Forbes hopes the findings encourage more researchers to explore bacterial approaches alongside other forms of immunotherapy and targeted therapy. “I want people to see the massive ways that we could treat cancer,” he said. “There are a lot of possibilities that I think are untapped.”

The post Engineered <i>Salmonella</i> Delivers Cancer-Killing Virus to Tumors appeared first on Inside Precision Medicine.

The findings, in Cell Host & Microbe, suggest extra benefits from this new class of drugs, beyond their metabolic effects on diabetes and obesity.

The GLP-1 receptor agonist liraglutide appeared have mental health benefits on mice, influencing brain function and behavior and reducing symptoms of depression.

This related to an increase in the abundance in the microbe Lactobacillus delbrueckii, which is known to act positively on neurons relating to stress.

Researcher Yonggui Yuan, PhD, from Southeast University in Jiangsu, China, noted mixed results from previous studies into the antidepressant effects from GLP-1 agonists.

“The prevailing model held that these drugs act directly on GLP-1 receptors in the brain, while our study provides evidence for an alternative pathway,” he said.

Emerging evidence suggests this drug class may exert biological effects beyond GLP receptors, such as reducing neuroinflammation after stroke or protecting against cisplatin-induced kidney injury.

The researchers therefore examined the neuropsychiatric effects of liraglutide and found that it had antidepressant effects that remained in mice deficient in the GLP-1 receptor.

The team identified a pathway independent of the GLP-1 receptor through which liraglutide could alleviate depressive-like behaviors in the animals.

Liraglutide encouraged the growth of L. delbrueckii by improving bacterial biosynthesis of serine and phosphoenolpyruvate (PEP), two metabolites that occupy pivotal roles in bacterial central metabolism.

PEP serves as a precursor for biosynthesis of amino acids, nucleotides, and cell wall components while the amino acid serine is a key node in one-carbon metabolism and a precursor for glycine, cysteine, and phospholipid synthesis, all essential for rapid bacterial proliferation.

Increasing levels of L. delbrueckii aided the production of diacylglycerol via triacylglycerol lipase.

This provided a precursor by which the animals could synthesize 2-arachidonoylglycerol (2-AG) levels, to normalize neuronal activity in emotional brain regions.

Gut-derived 2-AG inhibited stress-induced neuronal hyperactivity in the basolateral amygdala and dorsomedial hypothalamus, revealing a microbiota-endocannabinoid axis for potential use in depression therapy.

“Given the growing clinical use of GLP-1R agonists for metabolic disorders and the high comorbidity between metabolic and psychiatric conditions, understanding these pleiotropic, microbiota-mediated effects has important translational implications,” the authors noted.

“More broadly, the demonstration that a clinically approved metabolic drug can exert neuropsychiatric effects through microbiota-dependent mechanisms opens new avenues for drug repurposing and suggests that the therapeutic potential of existing pharmacological agents may extend far beyond their originally intended targets,” the authors concluded.

The post GLP-1s May Benefit Mental Health Through Gut–Brain Axis appeared first on Inside Precision Medicine.

“When I saw the Tune data on the long-term silencing of an infected cell line for 500 days, I realized it had never been seen before,” McHutchison told Inside Precision Medicine. “I was at Gilead for ten years, where I was head of research and development and worked on all the other viruses, including hepatitis C (HCV)… We spent a decade at Gilead trying to silence this mechanism without success.”

McHutchinson decided to get plugged into Tune Therapeutics, which was founded by Akira Matsuno, Charles Gersbach, PhD, and Fyodor Urnov, PhD, to develop epigenetic therapies that precisely control gene expression without altering DNA sequences. In January 2023, McHutchinson joined Tune’s board of directors and, two years later, became CEO and chairman in March 2025. That preclinical silencing has now shown promise in translating to the clinical setting.

Last month at the European Association for the Study of Liver (EASL) Congress in Barcelona, Spain, Tune presented the first clinical evidence of epigenetic silencing in HBV. The Phase Ia/IIb clinical data shows deep and durable antiviral activity, including silencing of both the integrated virus and covalently closed circular DNA (cccDNA)—a stable viral mini-chromosome that resides inside liver cell nuclei and continually produces new virus particles—offering a possible pathway to a lasting therapeutic effect for HBV patients.

“Now we have the data that shows we can durably silence a gene of interest in humans by modulating epigenetics without cutting,” McHutchison said. “That’s a big deal. The de-risking of the technology.”

Swimming upstream

More than 240 million people worldwide live with chronic HBV infection. Current antiviral therapies can suppress viral replication for years, sometimes decades, but they rarely eliminate the virus entirely. Once treatment stops, viral replication almost always returns. The central problem is cccDNA, often referred to as HBV’s “molecular reservoir,” which acts as a stubborn, self-renewing blueprint, making chronic HBV highly difficult to eradicate or cure.

“It’s also not lost on me that for a decade, our industry has poured billions of dollars into HBV, but without success,” said McHutchinson. “Why is that? Why didn’t we get there? Because we weren’t transcriptionally silencing the reservoir. We were working downstream.”

McHutchinson points out that even the most recent genetic medicines that have shown promise, such as the experimental HBV drug, an antisense oligonucleotide (ASO) called bepirovirsen developed by GSK, still work downstream. Bepirovirsen does not eliminate HBV’s reservoir of cccDNA inside liver cells. Instead, it targets and destroys HBV RNA transcripts, reducing viral replication and lowering the production of viral proteins such as HBsAg, while also helping restore immune responses against infected cells. Because the drug leaves cccDNA intact, its goal is not a cure at the genetic level but instead a functional one, where the immune system keeps the virus permanently suppressed or undetectable after treatment ends.

“You’d silence reverse transcription or cut it with siRNA, and things would fall in the serum, but you wouldn’t affect the reservoir,” said McHutchinson. “As soon as those drugs were removed, the reservoir started to make new viruses again. Nobody is, in essence, being cured. But here we’re working upstream, where the progeny and the new virus are being made.”

GSK may not see eye to eye with McHutchinson on bepirovirsen, which, according to a recent press release, “achieved functional cures in 19% of participants in two large Phase III trials when added to standard antiviral treatment for six months.” Chronic hepatitis B (CHB) is considered “functionally cured” when the blood has no detectable hepatitis B surface antigen or virus DNA for at least 24 weeks after a finite treatment course, allowing immune control without medication and reducing the risk of liver complications, including liver cancer, and all-cause mortality.

However, to McHutchinson, a functional cure and a genetic cure are apples and oranges. “That’s just stimulating an innate immunity,” he said. “It’s an injection a week for 24 weeks, and it’s an ISO that stimulates innate immunity—that’s why it’s curing one in five people who have low levels of HBV surface antigens. It’s a positive development for the field that something else could be approved. I speak admirably about that. But it’s not a panacea. And there’s a lot of room for many other people to come along with better things and better combinations.”

Durable biomarker suppression

Tune’s ongoing Phase Ib/IIa trial includes four dose levels of its therapy, administered as a single intravenous infusion, in 19 people. The dose cohorts ranged from 0.2 mg/kg to 0.85 mg/kg, as well as a multiple-dose cohort receiving up to three infusions. Another seven people got up to three infusions of the second-highest dose given at least four weeks apart, for a total of 26 participants, which McHutchinson acknowledged is quite small.

According to Tune, antiviral activity was seen across all major HBV biomarkers, including surface antigen (HBsAg), pregenomic RNA (pgRNA), e-antigen (HBeAg), HB core-related antigen (HBcrAg), and phosphorylated HBV core antigen. Tune reported that biomarker repression occurred in 100% of participants treated at dose levels two through four. Particularly striking were signs suggesting direct cccDNA silencing. Among HBeAg-negative patients treated at higher dose levels, four of seven lost detectable pgRNA, while three of those patients also lost HBcrAg. In HBeAg-positive patients, three of five lost detectable HBeAg.

McHutchison emphasized that the most encouraging signal may be durability. “Some of those patient graphs we showed have durability up to 250 or 300 days,” he said. “These genes have plateaued at very low levels and haven’t come back with a single application, which suggests and proves what we thought preclinically—that the methylation fingerprint and chromatin compaction are durable and don’t seem to leak or relapse.”

According to the company, suppression following a single dose has now been observed for as long as 17 months in some patients. As with any first-in-class therapy, safety remains a major focus. So far, Tune says TUNE-401 has shown a “favorable safety profile,” with mild to moderate infusion-related reactions, transient liver enzyme elevations, and temporary platelet reductions that resolved without major complications. “We have an acceptable and good safety profile compared to others,” McHutchison said. “What we are seeing in terms of AST and ALT elevations, infusion-related reactions, and transient reductions in platelets are pretty much in line with or better than what others are seeing with similar LNP products.”

Importantly, the company says it has not yet observed additive toxicity in patients receiving multiple doses. Whether multiple doses will ultimately be necessary remains uncertain. “There are examples in the presentation of a profound effect with a single dose and another patient who showed benefit from a second dose,” McHutchison said. “That’s still to be determined.”

Tune plans to continue dose optimization in Phase II, including testing additional multidose regimens and potentially escalating to even higher doses. “We’re tinkering with the maximum dose, trying to optimize it while keeping safety in mind,” he said.

Diversity, in patient and virus

The technology underlying TUNE-401 sits at the intersection of gene therapy, RNA therapeutics, and epigenetics. Rather than editing DNA permanently, the therapy uses a methyltransferase enzyme and the KRAB domain chromatin-compacting protein module to alter the epigenetic state surrounding HBV DNA.

“Once you’ve laid down that pattern, it is permanent and inheritable through cell division,” McHutchison explained. “We can vary the degree of silencing with our platform: 30%, 50%, 80%, or 100%. For hepatitis B, we tried for complete suppression.”

The concept of epigenetically programming cells has attracted growing interest across biotechnology, particularly as concerns remain about irreversible DNA editing approaches. “We feel, because we’re not editing, we can go after common diseases,” McHutchison said. “We’re looking at cardiovascular targets and a diabetes program as well. That’s what the technology can do without editing. But you have to get it there potently and safely.”

One of the key questions moving forward is whether the therapy will work consistently across the enormous genetic diversity of HBV strains worldwide. The current study spans sites in New Zealand, Hong Kong, and Moldova, intentionally capturing ethnically and geographically diverse patient populations. “There is viral diversity across various geographical areas, probably due to evolution and migration patterns over thousands of years,” McHutchison said. “We’ll be able to look at responses according to genotype.”

Tune estimates its targeting system covers approximately 98.5% of known HBV sequence variants based on historical databases. However, the company acknowledges that some patients in lower-dose groups showed weaker responses, raising questions about viral sequence variability. “We’ll be looking at whether there was a mutation or sequence difference from our target,” McHutchison said. Those analyses are expected later this year as additional viral sequencing data becomes available.

Addressing the applicability of TUNE-401 in diverse populations of people and viruses depends on something that Tune hasn’t yet got—numbers. That’s where GSK’s bepirovirsen holds a massive edge, with the two Phase III efficacy trials having involved more than 1,800 participants in 29 countries. The trial for TUNE-401 reported data from about 1–2% of GSK’s entire cohort.

A potential turning point

For McHutchison, the development path may resemble the evolution of HCV treatment, where he played a central role during his years at Gilead. He points to Pharmasset and the development of sofosbuvir (Sovaldi), a direct-acting nucleotide analog that blocks the virus’s essential protein (NS5B polymerase), which became the backbone of curative HCV regimens. “People forget that Sovaldi didn’t work that well by itself initially,” McHutchison said. “It had to be combined with ribavirin and interferon. But it was the backbone mechanism. I think in essence we have that backbone mechanism here.”

TUNE-401 could serve as the foundation for combination regimens capable of delivering a total remission from HBV. The company plans to initiate a larger Phase II study as early as late 2026, exploring combinations alongside optimized dosing schedules. “The approval endpoint for a finite HBV therapy is to drive these biomarkers negative, remove background therapy, and make sure people don’t relapse,” McHutchison said.

Many hurdles remain before TUNE-401 could approach regulatory approval. The current data comes from a small early-stage trial, long-term durability remains unproven, and the field has seen many HBV programs falter after initially promising signals. Still, the idea of directly silencing cccDNA—rather than merely suppressing downstream viral activity—represents a conceptual shift that many hepatologists have sought for decades.

“Over the prior 30 years in hepatology, I have rarely seen a clinical signal this clear,” McHutchison said.

The company’s broader ambitions extend beyond infectious disease. Tune has previously disclosed programs in cardiovascular disease and type 1 diabetes, where epigenetic modulation could potentially alter cellular function without permanent genomic changes. Still, HBV offers perhaps the clearest proving ground for the platform because the virus depends so heavily on transcriptional activity from cccDNA.

Whether Tune’s epigenetic editing approach succeeds remains uncertain. But for a field long defined by incremental advances and repeated disappointments, the data presented in Barcelona may represent something increasingly rare in HBV research: a plausible new path towards a cure.

And for McHutchison, it closes a loop that began years earlier in Gilead’s hepatitis research labs. “We knew this mechanism mattered,” he said. “The technology just didn’t exist yet. Now it does.”

The post Phase Ib/IIa for Hepatitis B Epigenetic Silencer Shows Best-in-Class Potential appeared first on Inside Precision Medicine.

As reported in the journal Radiology, the study also showed that women were particularly badly affected and had an 81% increased risk for obstructive coronary artery disease if exposed to long-term air pollution.

“Even at exposure levels below current Canadian air quality standards, long-term air pollution was independently associated with more advanced coronary artery disease—suggesting current regulations may not be fully protective and that air pollution belongs alongside blood pressure, cholesterol and smoking as a modifiable cardiovascular risk factor,” said lead author Kate Hanneman, MD, associate professor at the University of Toronto, in a press statement.

The study included 11,128 people who underwent cardiac computed tomography (CT) scans who also had available data for air pollution exposure for around 10 years. The average age was 60 years and 52% were men.

In the cohort, median 10‑year exposures were 7.5 μg/m³ for PM2.5, a common measure of particulate air pollution and 13.4 ppb for nitrogen dioxide. These levels are relatively low compared with many historical and low‑/middle‑income settings but still above the latest World Health Organization guideline of 5 μg/m³ for PM2.5 and 5.3 ppb for nitrogen dioxide.

For each addition increment of PM2.5 (1 μg/m³) people in the study had had about 11% more calcium in their coronary arteries and 13% higher odds of having more atherosclerotic plaque. For each increment of nitrogen dioxide (1 ppb) small but measurable increases in calcium (aprx 1%) and plaque (about 4%) were seen in the coronary arteries of those exposed.

After taking into account age, risk factors, medicines, and other differences, each increment higher long‑term air pollution was linked to more severe, artery‑narrowing heart disease in women, but not in men. Each increment increase in PM2.5 was associated with an 80% higher chance of women having a dangerously narrowed coronary artery and each increase in nitrogen dioxide a 6% increased chance.

There was a similar trend in men, but it was not statistically significant after correcting for possible confounding factors.

“These findings add to the growing body of evidence identifying air pollution as a modifiable risk factor for atherosclerosis,” conclude the authors.

“Considering the epidemiologic data linking air pollution to cardiovascular events, these results reinforce the urgency of global public health initiatives aimed at improving air quality to reduce cardiovascular risk.”

The post Exposure to Moderate Air Pollution Raises Cardiovascular Disease Risk appeared first on Inside Precision Medicine.