Uncategorized - Relatix Health

May 13, 2026

Technique Yields Uniform, High-Quality, EVs at Scale

Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) play an outsized role in intracellular communications, influencing such functions as inflammation and tissue repair. With the possible applications of these small, membrane-bound particles growing, an efficient, cost-effective production method has been on drug manufacturers’ wish lists for some time.

A novel, streamlined chromatographic production and isolation method developed by scientists at Satorius BIA Separations in Slovenia may fulfill that wish, yielding uniform, high-quality EVs at scale. The method concentrates MSC-EVs directly from conditioned media. It also removes 97% of protein impurities and 95% of double-stranded DNA-related impurities, increasing their potential as therapeutics or drug delivery vessels.

Microcarrier + suspension

The method relies upon preferential exclusion chromatography, Katja Vrabec, head of product application area (EVs) at Sartorius, notes in a recent paper. In it, Vrabec and colleagues explain the method “uses monolithic hydroxyl columns to purify and concentrate the MSC-EVs,” and biochromatography analytics to track EV-specific surface antigens.

First, the team expanded the MSCs in growth media, and then produced the EVs in a lean media formulation to limit production of protein and particle contaminants. That part is standard.

Here’s what’s different: The scientists used a microcarrier-based system rather than flask-based 2D cultivation to scale the MSC cultures and increase the ratio of EVs to contaminants in conditioned media. They also used a suspension culture to enhance cell growth surface-to-volume ratios, and thereby increase EV yield. Then, they used a monolithic hydroxyl column to capture and purify the EVs directly from harvest.

Increasing cell density and the cell-to-impurity ratio lowers buffer consumption downstream and lays the groundwork for biomanufacturers to transition to a scalable bioreactor system.

Because the main impurities in EV harvests don’t interact with the chromatographic column in high-salt-binding conditions, the team recommends choosing a low-salt buffer for elution to reduce the need for buffer exchange before the polishing step. The optimal binding condition, they report, is “sodium citrate of 0.75M at pH 7.0.”

This research highlights the need to consider upstream and downstream processing as a cohesive system, to design a simple, scalable, holistic process, and to apply reliable analytics. This all is particularly challenging, the team admits, given “the heterogeneous nature of EVs and the presence of similarly-sized components in biological samples.”

The post Technique Yields Uniform, High-Quality, EVs at Scale appeared first on GEN – Genetic Engineering and Biotechnology News.

May 13, 2026

Machine Learning for Comparative Antidepressant Selection in Major Depressive Disorder: Systematic Review

Background: Major depressive disorder (MDD) affects approximately 1 in 6 adults during their lifetime, yet antidepressant selection relies predominantly on trial-and-error, with response rates of only 42% to 53%. While machine learning (ML) models have shown promise in predicting treatment outcomes, most focus on single treatments rather than comparative selection across therapeutic alternatives, limiting their clinical utility for the medication choice decisions that clinicians face in practice. Objective: This systematic review evaluates ML approaches that examine 2 or more pharmacological interventions for predicting treatment outcomes in MDD, with a focus on their capacity to facilitate comparative treatment selection between medications or medication classes for individual patients. Methods: Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we searched PubMed, Scopus, and Web of Science for studies published from 2015 to 2025. We included studies involving adults with MDD that used ML models to predict treatment outcomes across 2 or more pharmacological treatments and reported medication-specific prediction outcomes. Risk of bias was assessed using PROBAST-AI (Prediction Model Risk of Bias Assessment Tool for Artificial Intelligence). We conducted a narrative synthesis organized by modeling strategies, data integration approaches, validation methodologies, and performance patterns. Results: From 5370 initial records, 19 studies met the inclusion criteria, with dataset sample sizes ranging from 49 to 77,226 participants. Studies employed 3 distinct modeling strategies: drug-specific supervised models trained independently for each medication, subtype- or trajectory-based approaches using clustering methods to identify differential response patterns, and a unified differential prediction framework generating calibrated cross-treatment predictions. Performance varied substantially, with area under the curve values ranging from 0.59 to 0.95 and classification accuracies between 62% and 95.4%, though high performance was concentrated in studies with small samples, high-dimensional neurobiological features, and internal-only validation. Only 7 studies conducted external validation, which generally yielded more conservative performance estimates. Feature informativeness was more consistently associated with performance variation than algorithm complexity. Most studies did not formally distinguish between prognostic features predicting general outcomes and predictive features identifying differential medication responses, and none applied formal explainability techniques. Conclusions: ML for comparative antidepressant selection remains in an early stage of development. Only 1 study implemented a unified framework directly supporting patient-level treatment ranking. Key barriers to clinical translation include insufficient distinction between prognostic and predictive markers, limited cross-trial validation, near-absent calibration reporting, and absent explainability. Future research should prioritize unified comparative frameworks with calibrated predictions, rigorous external validation on diverse cohorts, explicit modeling of heterogeneous treatment effects, and integration of explainability into model development.
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May 13, 2026

“It Was Not a Cure”: Musunuru Cautions ASGCT on Baby KJ Promise

BOSTON – When Kiran Musunuru, MD, PhD, walked to the microphone to deliver remarks on behalf of the team that won the American Society of Gene and Cell Therapy (ASGCT) 2026 Catalyst Award, most of the thousands of attendees surely expected a feel-good speech.

After all, it was 12 months ago that Musunuru, addressing the same convention in New Orleans, shared the exciting news regarding the delivery of a bespoke base editor to an infant, Baby KJ, with a rare urea cycle disorder. Musunuru and his colleague, Rebecca Ahrens-Niklas, MD, PhD, were recently named to the TIME 100 Most Influential People of 2026. “A decade from now,” stated Nobel laureate Jennifer Doudna, PhD, “their names will be in medical textbooks, not only for Baby KJ, but for opening the door to personalized genetic medicine for thousands of children after him.”

Musunuru and Ahrens-Niklas, from the University of Pennsylvania and Children’s Hospital of Philadelphia (CHOP), respectively, were honored alongside Doudna’s colleague Fyodor Urnov, PhD (Innovative Genomics Institute) and Danaher Corporation, for building the remarkable academia-industry consortium that designed and delivered the gene editing therapy, resulting in Baby KJ’s discharge from CHOP and a wave of national television appearances.

Indeed, Musunuru opened his ASGCT remarks in upbeat mood. “The potential is there to [deliver personalized therapies] over and over again for hundreds of diseases centered in the liver.” But halfway through his speech, Musunuru’s tone changed. While most grateful for the recognition from ASGCT, he said it was important to always “be your own worst critic.”

“I’ll be brutally honest,” Musunuru said. Despite the unquestionable “enthusiasm and excitement” surrounding the Baby KJ story, “there are some profound limitations. It was not really science at all!” Musunuru continued. “It was not a clinical trial. It was not clinical research. It was not a cure.”

“The best we can say is we hope we’ve turned a devastating disease into a milder, manageable condition. But it’s too early to say that… This was a personalized N-of-1 therapy—we can’t say what this means for anyone.”

Drawing applause from the audience, Musunuru pushed on: “We mustn’t be snake oil salesmen or give false hope… We have a profound ethical responsibility not to mislead families over what is possible.”

“We don’t actually know anything,” Musunuru said. “We need to do clinical trials—scientifically and ethically.”

The path forward

Musunuru set the Baby KJ story in the broader context of his group’s work on phenylketonuria (PKU), one of the classic inborn errors of metabolism. A few years ago, Musunuru and Ahrens-Niklas set about designing gene editing therapies targeting the first and sixth most common PKU mutations using adenine base editors. (There are more than 1,000 known mutations that cause PKU.)

After testing in humanized mouse models, the researchers were delighted to see the phenylalanine levels rapidly drop to normal, sustained for the lifetime of the mice. Flush with funding from the Somatic Cell Genome Editing program at NIH, Musunuru and Ahrens-Niklas began talks with the U.S. Food and Drug Administration in February 2024 to settle the question: Do we need separate Investigational New Drug applications (INDs) for each PKU variant?

“It is basically the same drug, the same gene, the same disease, the same clinical endpoints. Can’t we cover both variants in a single IND and a single ‘umbrella’ clinical trial?” summarized Musunuru. The answer was “maybe”—the agency needed to consider the full implications of the proposal.

The Philadelphia team began to develop workflows for four more PKU mutations, leading them to propose an umbrella trial for a revised total of six variants. Following another meeting with FDA officials in early 2025, the response was extremely positive: a single IND application would be appropriate, with a single toxicology study conducted in a single species. The FDA also agreed to consider additional variants.

In parallel, Ahrens-Niklas and Musunuru were studying sick patients with urea cycle disorders. Although these are liver disorders, “the real harm happens in the brain,” Musunuru said, resulting from toxic levels of ammonia. Enter Baby KJ’s diagnosis with CPS1 deficiency, and the notion that there was chance to design a personalized therapy.

In the Fall of 2024, Musunuru and Ahrens-Niklas held a pre-IND meeting with FDA officials. The idea was to streamline applications for a group of urea cycle disorders caused by mutations in seven different genes.

The FDA judged that all seven therapies could be evaluated in a single Phase I/II trial, but separate INDs would be required for each gene. “We’d have to do it piece by piece,” Musunuru said. First, file a master protocol for urea cycle disorders; after that IND clears, then file additional gene-specific INDs and amend the original IND.

“This is how we can make the trial accessible to all UCD patients across the country,” he said.

Back to the future

Coming back to the present, Musunuru stated that although the primary IND had been filed, “this does not mean the trial is open or we can enroll patients.” Musunuru listed three major issues:

The team has not yet manufactured any gene therapy product.
As seven INDs are needed to fully open the clinical trial, it will be well into 2027 until all INDs are submitted.
In February 2026, the FDA issued a draft Plausible Mechanism Framework. Musunuru’s team held another pre-IND meeting with the FDA to advocate for the use of prime editing for urea cycle disorders. After all, Musunuru reasoned, why should therapies be restricted to base editing approaches (G-to-A substitutions) but not patients who harbor a G-to-C mutation? The FDA indicated that a separate IND/BLA would be needed for each gene, and that process validation should be finalized before any dosing of Phase II subjects.

The path forward, Musunuru said, was to adopt an adaptive, real-time clinical trial design. That involves testing therapies, then advancing therapies from proof-of-concept to the validation phase. At that point, if all goes well, they can submit a BLA. Ahrens-Niklas and Musunuru laid out more details of their approach and dealings to date with the FDA in a commentary published late last year entitled: “How to create personalized gene editing platforms.”

With that, Musunuru hastily closed and exited stage left to give a keynote address at another conference across the road.

The post “It Was Not a Cure”: Musunuru Cautions ASGCT on Baby KJ Promise appeared first on GEN – Genetic Engineering and Biotechnology News.

May 13, 2026

<![CDATA[“Because I’m a quiet man I listen before I speak, tune into my patient’s voice…”]]>

May 13, 2026

ASGCT 2026: Victoria Gray Roadshow Returns to Boston

BOSTON – The annual American Society of Cell and Gene Therapy (ASGCT) conference got underway in Boston this week with a guest appearance by one of gene therapy’s greatest ambassadors and patient advocates.

Victoria Gray, the sickle cell warrior who was successfully treated in the exa-cel clinical trial sponsored by Vertex Pharmaceuticals/CRISPR Therapeutics seven years ago, spoke in an evening workshop organized by the Emily Whitehead Foundation and ScaleReady.

Boston is becoming a regular stomping ground for Victoria. Last November, she spoke at the Genetic Agency Technology Conference, hosted by Dyno Therapeutics. Last month, she finally received an invitation to visit the headquarters of Vertex and speak in a town hall meeting.

In an extemporaneous 20-minute speech, Victoria talked about her lifelong journey with sickle cell disease (SCD). She recalled her first major pain crisis, when she was a young girl—a lightning-type pain that began in one arm before traveling across her chest and down the other arm. “In minutes, my entire body was engulfed in pain,” she said. “The pain felt like getting struck by lightning and hit by a truck. It took me to the floor.” Her grandmother provided hot towels and Tylenol, but nothing worked—not even prayer. After a week in hospital, Victoria returned home but still felt fatigued.

Stricken by regular pain crises, a hallmark of SCD, Victoria encountered numerous disappointments growing up. Her hematologist said she could not join the cheer team. In eighth grade, she was told she could not join the basketball team, because the exertion would provoke a pain crisis. “As a kid, I was like a Timex: I could take a licking and keep on ticking,” she joked.

In high school, she signed up to join the United States Navy. “I wanted to serve my country,” Victoria recalled. As she was preparing for basic training, she learned that her disease prevented her from enrolling. “So that was another dream lost.” Next, she turned her attention to nursing. Victoria graduated high school in 2003, but it took another seven years before she could qualify for a nursing program. “Professors didn’t understand because I looked whole and complete. They didn’t think I was sick.”

In 2010, just before Halloween, Victoria had the worst pain crisis of her life, stripping her ability to walk or use her arms to feed herself. “I couldn’t do anything, facing some of the worst pain of my life. I was getting strong pain medicines like Dilaudid, ketamine, but still couldn’t move. Pain had taken over my thoughts.” Unable to sleep or even take a nap, Victoria was desperate to go home to her family.

Later, she asked the doctors if they had heard about a haplo-bone marrow transplant (BMT). “I can’t continue living like this,” she said. The doctors looked at each other and said no. After weeks of prayer, Victoria received a call from her hematologist. “Victoria, I have good news, but I only want to tell you in person.” For the first time in her adult life, Victoria was excited about a doctor’s appointment.

She traveled to Nashville with her brother, who would be her BMT donor, and her husband. She met Haydar Frangoul, MD, whom Victoria calls, “the nicest doctor that I’ve met in my adult life.” Frangoul told her: “Victoria, I wish I had met you ten years ago!’

Although Victoria’s brother was a suitable BMT match, Victoria was scared of the possibility of graft vs. host disease (GVHD). “My purple pill basket was filled to the brim with medicine every day. If I would acquire [GVHD], that basket would have to triple in size.”

“I’m a human!”

On her next visit to Nashville, she had to extend her stay because of another pain crisis. But that stay changed her life. Frangoul sat next to her bedside. “Victoria, have you ever heard of CRISPR?” he asked. Victoria shook her head.

Frangoul used a typo-in-a-textbook analogy and reassured Victoria that there was no chance of GVHD, because she would be receiving her own modified stem cells. “You’ll be the first person to do this, Victoria,” he said. “First human?” she asked. “Yes,” Frangoul said, “but it’s been tested in primates.”

“But I’m a human!” she said.

After being reassured that she could still try a bone marrow transplant if the procedure did not work, Victoria agreed to move forward. The chemotherapy, was “hell on Earth,” she recalled. “I lost my hair, which I was prepared for, but the mucositis, the sores in my mouth, the inability to eat for two weeks, was gruesome.”

Victoria swallowed her tears and decided to fight. This was the first time she had been in the hospital by her choice, to live for her children. About eight months after receiving her CRISPR-edited stem cells in July 2019, she woke up one morning, not feeling anything. “Oh my God, I’m dead,” she thought. She called her kids into the room and hugged them, slowly realizing that “this is what normal feels like.” For the first time in more than 25 years, Victoria did not have any pain in her lower back and hips. She was able to breathe deeply without wincing.

A few years after her therapy, Victoria was finally able to take her first ever flight, to Washington D.C. to visit her husband, who was on deployment. “It was the first time that I was ever able to show up for the man who has shown up for me,” she said. She has since watched her daughter dance in a Christmas parade and supported her son playing high school football. “The little things have brought me great joy,” she said.

Her second flight was a business class trip to London with her husband in March 2023, where she spoke at the third International Summit on Human Genome Editing. “I got to keep my covenant that I made with God, that God, if you do this for me, I would tell the world about what you did.”

Victoria welcomed her first granddaughter on Christmas Eve, 2024. Next week, another milestone: she will be in the audience as her twins graduate high school. And next month, she will publish a children’s book called Hema’s Journey, the tale of her inspiring journey with CRISPR gene therapy. She’s currently training for a group effort to climb Mt. Kilimanjaro.

Perhaps at next year’s ASGCT conference in Philadelphia, she will be invited to present in a plenary session on the main stage. It would be hard to think of a more fitting speaker.

The post ASGCT 2026: Victoria Gray Roadshow Returns to Boston appeared first on GEN – Genetic Engineering and Biotechnology News.

May 13, 2026

<![CDATA[Experts discuss rapid cycling and bipolar II, and weigh lithium as an often overlooked treatment option. ]]>

May 13, 2026

Regional Virtual Acute Care Helpline in Singapore at a National University Health System Virtual Care Centre: Retrospective Study

Background: Emergency department (ED) overcrowding and delayed access to care are ongoing challenges in Singapore. The COVID-19 pandemic further underscored the need for scalable virtual care models that go beyond traditional hospital settings, allowing patients to access acute specialist care quickly and efficiently. Objective: This study describes the design, implementation, and early outcomes of the National University Health System (NUHS) Virtual Care Centre (VCC), a clinician-led helpline aimed at reducing unnecessary ED visits and supporting community-based acute care. Methods: In 2020, the NUHS launched the VCC, a helpline at Alexandra Hospital, as a prehospital triage model. The helpline functions as a nurse-led telephone triage with real-time escalation to doctors for urgent medical issues. It ensures the continuity of care for patients recently discharged and diverts nonemergency cases from the ED. A retrospective analysis of call data from 2020 to 2024 was conducted to evaluate utilization patterns, clinical outcomes, and safety. Results: Over 4 years, the VCC managed 4857 calls, of which 59.3% (n=2879) were clinical in nature. Nearly two-thirds (1834/2879, 63.7%) were resolved remotely, preventing in-person ED visits. Only 13.8% (397/2879) required redirection to an ED, and 3.3% (95/2879) were directly admitted to an acute hospital or hospital at home service. Within 72 hours of call resolution, 69.1% (1990/2879) of the callers avoided an ED visit. Undertriage was 4.9% (110/2232) at 72 hours post call resolution, with no high dependency or intensive care unit admissions during this period. Mortality rates were low (1.0% at 14 days; 2.3% at 30 days). Conclusions: The NUHS VCC provides a feasible and safe model for virtual acute care triage within the public health care system. It effectively diverted lower-acuity cases from the ED and ensured continuity of care, offering a scalable approach aligned with national efforts to extend health care beyond hospital walls.
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May 13, 2026

<![CDATA[A new report shows private practice clinicians deliver over 113 million sessions of mental health care, making up the majority of outpatient care.]]>

May 13, 2026

iCARE Self-Guided Digital Intervention for Postpartum Depression in Danish Mothers: Formative Research Using User-Centered Design

Background: Postpartum depression (PPD) is a major public health concern. Despite advancements in treatment, many barriers to accessing care remain. There has been a growing interest in digital interventions for the prevention and treatment of PPD. However, for mothers with mild and moderate symptoms of depression, there is a limited offer of self-guided internet-based interventions developed with user input and with considerations on how to integrate the intervention into stepped care models for PPD. Objective: The aim of this study was (1) to describe the process of the design and development of iCARE, a self-guided digital psychological intervention for mothers with mild and moderate symptoms of PPD in Denmark, (2) present the program’s theory illustrated by a logic model, and (3) explore its initial usability and prospective acceptability. Methods: Applying user-centered design methods, the intervention development followed six steps: (1) a literature review to identify evidence‑based therapeutic components of self‑guided interventions for PPD, (2) interviews with women with lived experience of PPD and group discussions with mental health experts and home‑visiting providers to identify user needs, (3) iterative design and content development with stakeholder feedback in collaboration with the Department of Digital Psychiatry, (4) prototype testing using think‑aloud usability sessions and interviews with 5 mothers, (5) a group cognitive walkthrough with mental health experts, and (6) final refinement and implementation of the iCARE program with developers and designers. Results: Initial interviews with mothers and maternal health care providers emphasized the importance of a digital intervention offering timely psychoeducation, coping strategies, and pathways to in-person care while addressing the diversity of expressions of PPD symptoms. Stakeholders recommended a flexible program, multimodal content, and integration into maternal care systems with community health nurses supporting engagement and participation. The prototype was designed to be user-centered, engaging, and with multiple interactive features. It included components on psychoeducation, cognitive exercises grounded in cognitive behavioral therapy, acceptance and commitment principles, and mood-monitoring. The prototype was designed to be user-centered and engaging, with interactive features and components on psychoeducation, cognitive exercises grounded in cognitive behavioral and acceptance and commitment principles, and mood-monitoring. Prototype testing indicated high prospective acceptability and led to refinements across 6 themes: appropriateness of content; motivation and engagement; inclusivity and gender representation; clarity of instructions and data use; understanding of therapeutic method; and usability, layout, and navigation. Conclusions: iCARE is a self-guided internet-based psychological intervention for mothers with mild and moderate symptoms of PPD in Denmark. It was developed with user input by using qualitative methods, user-centered design, and psychological theory. Further research is needed to evaluate the feasibility and effectiveness of the program in a randomized controlled trial and its integration into maternal health care models such as universal PPD screening and home-visiting.

May 13, 2026

Early Detection of Alzheimer’s Disease and Related Dementias From Spontaneous Speech Using Foundation Speech and Language Models: Comparative Evaluation

Background: Alzheimer’s disease and related dementias (ADRD) are progressive neurodegenerative conditions where early detection is critical for timely intervention and care planning. However, current diagnostic methods are often inaccessible, costly, and delayed, especially for underserved populations. There is a growing need for scalable, noninvasive tools that can support timely diagnosis. Spontaneous speech contains rich acoustic and linguistic markers that can serve as noninvasive behavioral markers for cognitive decline. Foundation models, pretrained on large-scale audio or text data, generate high-dimensional embeddings that encode rich contextual and acoustic information. Objective: This study benchmarks open-source foundation language and speech models to evaluate their effectiveness in detecting ADRD from spontaneous speech as a potential solution for early, noninvasive, and scalable ADRD detection. Methods: In this study, we used the Pioneering Research for Early Prediction of Alzheimer’s and Related Dementias EUREKA (PREPARE) Challenge dataset, which consists of audio recordings from over 1600 participants with 3 distinct categories of cognitive decline: healthy control (HC), mild cognitive impairment (MCI), and Alzheimer’s disease (AD). We further excluded samples that are non-English, nonspontaneous speech, or of poor quality. Our final samples included 703 (59.13%) HC, 81 (6.81%) MCI, and 405 (34.06%) AD cases. We systematically benchmarked 18 open-source foundation speech and language models to classify cognitive status into 3 categories (HC, MCI, or AD). Post hoc interpretability analysis was performed for the best-performing model using Shapley additive explanations linking high-dimensional embeddings with explainable acoustic and linguistic markers. Results: Whisper-medium model achieved the highest performance among speech models at 0.731 accuracy and 0.802 area under the curve, while Bidirectional Encoder Representations from Transformers with pause annotation achieved the top accuracy of 0.662 and 0.744 area under the curve among language models. Overall, ADRD detection based on state-of-the-art automatic speech recognition model-generated audio-embeddings outperformed other models, and the inclusion of nonsemantic information, such as pause patterns, consistently improved the classification performance of text-embedding–based models. Conclusions: Our work presents a comprehensive comparative evaluation of state-of-the-art speech and language models for AD and MCI detection on a large, clinically relevant dataset. Embeddings derived from acoustic models, which capture both semantic and acoustic information, show promising performance and highlight the potential for developing a more scalable, noninvasive, and cost-effective early detection tool for ADRD.