Background: There is a need for scalable and simple interventions for trauma-exposed people. In this case series, we built on our previous case study and case series findings and further explored the use and potential effectiveness of a brief novel intervention to reduce the number of past intrusive memories of trauma. The imagery competing task intervention consists of a memory reminder and the visuospatial task Tetris played with mental rotation, targeting 1 intrusive memory at a time. Here, we test remote delivery of the intervention, including guidance from researchers without specialist mental health training, in a sample of women in Iceland with current intrusive memories from trauma. Objective: In a case series of trauma-exposed women, we aimed to explore whether this brief novel intervention reduces the number of established intrusive memories (primary outcome) and improves general functioning and symptom reduction in posttraumatic stress, depression, and anxiety (secondary outcomes). The acceptability of the intervention along with adaptations, that is, delivery by psychology students without specialist mental health training and digital delivery, was explored. Methods: Participants (N=8) monitored the number of intrusive memories from an index trauma (occurring 3‐16 years previously) in a daily diary at baseline, during the intervention, and postintervention at 1-month and 3-month follow-ups. The intervention was delivered digitally with guidance from clinical psychologists or psychology students. A repeated AB design was used (“A”: preintervention baseline, “B”: intervention phase). Intrusions were targeted one by one, creating repetitions of an AB design (ie, length of baseline “A” and intervention “B” varied for each memory). Results: The number of intrusive memories reduced for all participants from the baseline phase compared with the intervention phase, although the reduction was minimal for 2 participants (6.3%‐93%). The number of intrusive memories continued to reduce for 6 out of 8 participants (58%‐100% reduction at 1-month follow-up; 72%‐100% reduction at 3-month follow-up). Symptoms of posttraumatic stress, depression, and anxiety were reduced for most participants postintervention and continued to decrease during the follow-up periods. Functioning was improved for 7 of the 8 participants from baseline to postintervention and continued to improve at the follow-up assessments for 3 participants. The intervention delivered digitally and partly by students was perceived to be an acceptable way to reduce the frequency of intrusive memories by all participants (mean rating 9.5 out of 10). Conclusions: Data from this case series of traumatized women provide preliminary evidence for the effectiveness of this novel brief intervention in reducing intrusive memories of trauma occurring several years ago and in improving functioning and reducing core symptom burden. This study will inform a randomized controlled trial of this novel intervention, which may have considerable implications for large-scale clinical management of traumatized populations. Trial Registration: ClinicalTrials.gov NCT04209283; https://clinicaltrials.gov/study/NCT04209283 International Registered Report Identifier (IRRID): RR2-10.2196/29873
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<![CDATA[Phase 2 MINDFuL data show XPro trends toward cognitive and biomarker gains in inflammation-defined mild Alzheimer disease, with no ARIA, guiding phase 3 plans.]]>
Favipiravir for Lassa fever: an open-label, randomized controlled phase 2 trial
Nature Medicine, Published online: 15 May 2026; doi:10.1038/s41591-026-04402-w
An open-label, randomized controlled phase 2 trial comparing favipiravir with ribavirin for the treatment of mild-to-moderate Lassa fever in Nigeria found that favipiravir was safe and well tolerated and supports its further optimization as a treatment alternative.
HIV and Substance Use Reduction for Youth Experiencing Homelessness: Development and Usability Study
Background: Youth experiencing homelessness face heightened vulnerability to HIV infection and substance use due to complex structural, psychosocial, and behavioral factors. Despite increased mobile phone access among youth experiencing homelessness, few mobile health interventions have been tailored to their unique needs, and even fewer have applied behavioral theory to inform message development. Objective: This study aimed to develop and refine theory-driven, tailored HIV prevention and substance use reduction messages for use in a just-in-time adaptive intervention app, MY-RIDE (Motivating Youth to Reduce Infections, Disconnections, and Emotional dysregulation), designed for youth experiencing homelessness aged 18 to 25 years. Methods: This study was conducted in 4 phases: prevention messages were developed and pilot-tested in 2018 (phase 1), revised and expanded using the experience and expertise of content experts and the study team (phase 2), reviewed for relevance and acceptability by youth experiencing homelessness in 2024 (phase 3), and supplemented with messages generated using an artificial intelligence (AI) tool (phase 4). Results: Phase 1 resulted in the development of 386 intervention messages across 7 content categories: sex urge, drug and alcohol urge, stress, drug use, recent sexual activity, recent sexual assault, and general motivational messages. During phase 2, the study team expanded the message library to 888 messages across 10 categories. During phase 3, the youth working group liked 93% (803/864) of messages reviewed, which were categorized as acceptable for the intervention. Disliked messages were discarded and replaced with messages generated by an AI tool in phase 4. Conclusions: The finalized set of intervention messages was integrated into the MY-RIDE app to support personalized, real-time intervention delivery. Codeveloping messages with youth experiencing homelessness and leveraging AI tools proved feasible and effective for tailoring HIV prevention and substance use content. This approach supports scalable mobile health interventions for marginalized populations and informs future efforts to design engaging, theory-based digital health strategies. A randomized controlled trial of the MY-RIDE intervention is underway. Trial Registration: ClinicalTrials.gov NCT06074354; https://clinicaltrials.gov/study/NCT06074354
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STAT+: Biogen’s tau-targeting Alzheimer’s drug posts mixed results in mid-stage study
Biogen reported mixed results Thursday from a mid-stage clinical trial investigating a treatment for Alzheimer’s disease that targets the protein tau that, like the better-known amyloid, is toxic to neurons and is believed to play a role in the cognitive decline of patients with the disease.
In the Phase 2 study, the Biogen drug, called diranersen, or BIIB080, reduced levels of tau in the spinal fluid and brains of patients with early-stage Alzheimer’s. Those tau reductions also correlated to a slowing of cognitive decline, the company said.
Biogen investigated three escalating dosing regimens in its study, with the lowest dose showing the best results. For that reason, the study failed to achieve its primary efficacy goal, which was a dose response.
STAT+: Regenxbio says Duchenne gene therapy succeeded in clinical trial, paving way for FDA submission
Regenxbio said Thursday that its experimental gene therapy for Duchenne muscular dystrophy produced sufficiently high levels of a miniaturized muscle protein broken in the fatal neuromuscular disease, paving the way for a submission to the Food and Drug Administration.
The company is seeking to create a Duchenne gene therapy that is more effective and safer than Sarepta Therapeutics’ Elevidys, which has been hampered by safety concerns, particularly following the deaths of two recipients from liver failure.
“I think our data checks every single box that you would want for accelerated approval,” Regenxbio CEO Curran Simpson told STAT.
“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.
Orforglipron for maintenance of body weight reduction: the double-blind, randomized phase 3b ATTAIN-MAINTAIN trial
Nature Medicine, Published online: 13 May 2026; doi:10.1038/s41591-026-04386-7
As presented at the European Congress on Obesity, this randomized, placebo-controlled trial demonstrates that oral orforglipron, a nonpeptide GLP-1 receptor agonist, preserves weight loss and cardiometabolic benefits achieved with injectable GLP-1 receptor agonist therapies, making it a viable oral maintenance strategy.
Pasteurized Akkermansia muciniphila MucT for weight loss maintenance in people with overweight and obesity: a controlled randomized trial
Nature Medicine, Published online: 13 May 2026; doi:10.1038/s41591-026-04394-7
In a randomized trial, pasteurized Akkermansia muciniphila improved weight loss maintenance and metabolic health after a low-energy diet, especially in individuals with initially lower Akkermansia levels. The work suggests leveraging gut A. muciniphila as a potential target for weight management.
Low‑Dose Digoxin Shows Benefit in Heart Failure Treatment
Prescribing low-dose digoxin for patients with heart failure may reduce hospitalizations and cardiovascular complications when the drug is added to current guideline-directed therapy, according to three studies led by researchers at the University Medical Center Groningen (UMCG). The findings, published in Nature Medicine, showed that a meta-analysis combining data from the DECISION clinical trial with two earlier randomized studies found hospitalizations were reduced by 25% achieved by a reduction in worsening heart failure events.
Heart failure affects roughly 60 million people worldwide. Standard treatments currently rely on four medications commonly referred to as the “Fantastic Four.” The Groningen investigators examined whether digoxin, a drug that has been used for centuries in cardiovascular medicine, could serve as an additional therapy alongside those treatments.
The core study in the newly published research was the randomized, double-blind, placebo-controlled DECISION trial, which enrolled 1,000 patients with symptomatic chronic heart failure and a left ventricular ejection fraction of 50% or less at 43 centers in the Netherlands. Participants received either low-dose digoxin (600) or placebo (400) in addition to standard therapy with a median follow-up of 36.5 months.
The trial found that low-dose digoxin reduced the combined rate of worsening heart failure events and cardiovascular mortality by 19%, a figure that was not statistically significance. But when these data were then combined with two earlier randomized trials that evaluated digitalis glycosides—the same class of drugs as digoxin—in heart failure, the pooling of data from the three studies was able to demonstrate a statistically significant benefit.
The data from DECISION showed 238 primary outcome events among patients receiving digoxin compared with 291 events in the placebo group. The number of worsening heart failure events was also lower in the digoxin arm, with 155 events compared with 203 among placebo-treated patients.
One of the earlier studies, the DIG trial, published in 1997, had researched digoxin in patients receiving diuretics and angiotensin-converting enzyme inhibitors. While this combination did not reduce all-cause mortality, it demonstrated a 28% reduction in hospitalization for worsening heart failure. Subsequent analyses of the DIG data also suggested that lower serum digoxin concentrations were associated with more favorable outcomes, while higher concentrations above 1.2 ng ml−1 were linked to increased mortality.
The other earlier study, DIGIT-HF, had evaluated low-dose digitoxin added to contemporary heart failure therapy. In this study, the researchers reported a 15% reduction in the combined endpoint of all-cause death and first hospitalization for heart failure.
The third and current study from the Groningen researchers followed about 600 patients who had participated in the DECISION clinical trial after study treatment ceased. In this case, the team found that patients who discontinued digoxin experienced more problems during the first six weeks after withdrawal than patients who had never received the drug. Among 288 patients who stopped digoxin, 14 were hospitalized or died.
The studies all focused on low-dose digoxin because earlier analyses had suggested that lower serum concentrations of the drug produced benefit without the adverse effects created by higher dosing levels. In the past, higher doses were used to increase heart muscle contraction, but the researchers found that this approach was not beneficial in weakened hearts. Instead, lower doses appear to blunt adverse compensatory responses in heart failure.
The DECISION study also provided new randomized data regarding the safety of low-dose digoxin in women and in patients with atrial fibrillation, populations that had been considered at risk from higher doses. The investigators reported that low-dose digoxin did not increase adverse effects or pacemaker implantation and produced similar findings in men and women.
These new data could change heart failure guidelines in the future by including the use of digoxin as an additional therapy in patients with reduced or mildly reduced ejection fraction. Further, because digoxin therapy costs less than ten cents per day, it could offer a low-cost treatment option compared with newer therapies that cost several dollars daily.
The researchers said future work should further define which heart failure populations benefit most from low-dose digoxin and continue evaluating its role alongside contemporary guideline-directed therapies, including sodium-glucose cotransporter-2 inhibitors and other newer agents.
The post Low‑Dose Digoxin Shows Benefit in Heart Failure Treatment appeared first on Inside Precision Medicine.