Tag: Academic research

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STAT+: Drug meant to make gene therapy safer may also make it less effective

BOSTON — A medicine increasingly used to mitigate the risk of deadly gene therapy side effects could also blunt the therapy’s effectiveness, a new study finds.

The trial, from the startup Encoded Therapeutics, tested a gene therapy for Dravet syndrome, a severe form of genetic epilepsy. A key concern in gene therapy trials is that patients could mount an immune response against the engineered viruses used to deliver new genes into the brain. 

In the study, Encoded assigned most of the 21 children in the trial to receive steroids, the most commonly used immune suppressant. A subset — including most of the patients on the highest dose level — were assigned to also receive sirolimus, also known as rapamycin, a drug historically given to prevent rejection in transplant recipients. 

Continue to STAT+ to read the full story…

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10x Genomics, Harvard Target Element’s Multiomics Platform in Patent Lawsuit

10x Genomics and Harvard University have sued Element Biosciences, alleging that Element’s AVITI24™ multiomics platform, Teton chemistry, and related services infringe on four university-owned patents exclusively licensed by the genomics and sequencing tools giant—while Element has denied wrongdoing and promises to fight the lawsuit.

At issue are four patents—three of which cover technologies related to methods of analyzing the nucleic acids of a cell, awarded between 2021 and 2023, and all titled, “Compositions and methods for analyte detection”: U.S. Patent Nos. 11,021,737 (‘737), 11,566,276 (‘276), 11,566,277 (‘277).

The fourth patent in question, U.S. Patent No. 12,264,358 (‘358), covers methods of selectively sequencing amplicons in a biological sample, and was awarded in April 2025 under the title, “Method of selectively sequencing amplicons in a biological sample.”

“Element’s employees, customers, collaborators, and partners have practiced and continue to practice (with Element’s knowledge) one or more claims of the Harvard patents by using the AVITI24 platform and Teton workflow,” 10x and Harvard alleged in a court complaint filed May 7 in U.S. District Court for the District of Delaware. “Through the development and subsequent making, using, selling, offering for sale, and/or importing of the Accused Instrumentalities, Element has and continues to infringe the Harvard Patents.”

At the deadline, the case, 1:26-cv-00538-UNA, had not been assigned to a U.S. District Judge.

10x and Harvard have asked the court to find that Element infringed the four patents in question, declare that Element’s infringement “has been willful and deliberate;” declare each Harvard-owned patent to be “valid and enforceable;” issue a permanent injunction barring Element from using technologies based on the patents—otherwise pay 10x and Harvard “an award of post-judgment royalty to compensate for future infringement;” as well as require Element to pay 10x’s and Harvard’s attorneys’ fees and “such other and further relief as the Court may deem just, reasonable, and proper.”

Element responds

Element responded to the complaint a day later with a statement denying wrongdoing and promising to fight the lawsuit.

“Element strongly disagrees with the allegations made by 10x Genomics and believes the claims are without merit,” the firm stated. “Element will vigorously defend its technology and remains focused on delivering differentiated solutions that expand scientific discovery and customer choice. Element was founded to expand innovation and competition in the life sciences industry. We remain confident in our technology, our intellectual property, and the differentiated value our products provide to customers,” the company added. “We will continue to focus on supporting our customers and advancing the next generation of scientific innovation.”

AVITI24, launched in 2024 as a top-tier successor to its AVITI™ benchtop DNA sequencer and introduced two years earlier as a next-gen sequencing (NGS) platform, aims to enable simultaneous analysis of multiple biological signals—DNA, RNA, proteins, phosphoproteins, and cell structure within single cells—through a 5D multiomics system designed to deliver both spatial, single cell multiomics as well as high-quality, affordable sequencing.

Earlier this year, Element announced plans to begin offering Direct In Sample Sequencing to tissue—both FFPE and fresh frozen—during the second half of this year through AVITI24. “By contrast, 10x’s Xenium product included fresh frozen and FFPE tissue capabilities at the time it was introduced in 2022,” 10x countered in the complaint.

Element has applied AVITI24 to offer customers a combined in situ multiomics and next generation sequencing service through its AVITI24 Technology Access Program.

“Element practices the Harvard patents by using the AVITI24 platform on behalf of its own scientists and researchers and for its AVITI24 TAP customers,” 10x and Harvard alleged in their complaint, adding: “Through the AVITI24 TAP, customers submit samples to Element. Element practices the Harvard Patents by analyzing the samples using the Teton workflow on the AVITI24 platform.”

Stifling or protecting?

In its statement, Element also repeated an argument made by several other companies sued by 10x in recent years: “We believe this lawsuit yet again reflects a broader pattern of using the same patent portfolio to stifle innovations across the industry.”

Countered Michael Schnall-Levin, 10x’s chief technology officer, chief strategy officer, and founding scientist: “We strongly disagree with that characterization. 10x welcomes competition and innovation. “Over the past decade, we’ve invested more than $2 billion in R&D that has transformed how biology is studied. Protecting that work is part of our responsibility as innovators and is what enables us to continue investing in the next generation of technologies.”

Element is the latest of 10x’s rivals to find itself the target of a patent infringement lawsuit filed by 10x. Last year, 10x settled separate lawsuits with Vizgen and Bruker—the latter acquiring NanoString in 2024 from U.S. Bankruptcy Court after the company sought protection from creditors under Chapter 11 of the U.S. Bankruptcy Code, blaming a $31 million jury award assessed against it in 2023 in a patent infringement case filed by 10x.

In October, 10x joined with two licensor partners, Prognosys Biosciences and Roche Sequencing Solutions, to file a pair of federal lawsuits accusing sequencing and multiomics giant Illumina of infringing on nine patents related to spatial biology and single-cell sequencing. Earlier last year, Illumina sued Element, accusing its smaller rival of infringing on five of its patents covering flow cell and imaging technologies used in automated genetic sequencing.

Schnall-Levin said 10x’s latest wave of litigation, starting last year, was not a response to competitive pressures the company has discussed publicly, such as academic customers slowing down spending due to federal budget cuts: “Our litigation is driven by the merits of each case based on clear evidence of others infringing our patents.”

“We consistently act when others infringe our single cell and spatial patents,” Schnall-Levin added.

Speaking with GEN last year, Serge Saxonov, PhD, co-founder and CEO of 10x Genomics, defended the company’s approach to protecting its intellectual property: “If others end up infringing and copying our inventions, then we have to protect them. It is incumbent on us, both as a means of serving our mission and as a means of being fair to all our stakeholders.”

Patents detailed

In their lawsuit, 10x and Harvard allege that the ‘358 amplicon sequencing patent’s claims cover “concrete, unconventional” methods for sequencing RNA molecules in cell or tissue samples by generating circularized RNA molecules by crosslinking or copolymerizing circular DNA, amplifying the circular DNA to produce amplicons, then using selective sequencing primers to sequence different subsets of the amplicons at a time: “These additional unconventional combinations include sequencing by synthesis (Claim 15) and using at least sixteen different selective sequencing primers (Claim 18).”

The other three patents, which cover analyte detection, include claims directed to “concrete, unconventional methods that cover:

  • ‘276: multiplex detection of analytes in biological samples by contacting the biological sample with ‘detection reagents.’
  • ‘277: multiplex detection of analytes in cell and tissue samples by binding ‘detection reagents’ to the cell or tissue sample.
  • ‘737: Multiplex detection of analytes in cell and tissue samples by contacting the cell or tissue sample with ‘detection reagents.’”

10x says the methods of all three patents are practiced by its two spatial biology platforms—the Xenium In Situ single-cell spatial imaging platform, launched in December 2022, and the Atera spatial platform, unveiled last month during the American Association for Cancer Research (AACR) conference.

Atera, which is designed to enable whole-transcriptome spatial biology at scale, offers more plex, throughput, and sensitivity than Xenium, thus enabling whole-transcriptome at scale. Atera includes an all-in-one instrument for sample imaging, liquid handling, hardware stabilization, and onboard analysis.

According to 10x, Atera enables 800 whole transcriptome samples per year, a 500 mm2 imageable area per slide, and four slides per instrument run. Users can choose from Atera WTA, which allows for analysis of 18,000 genes, or Atera Select 1,000 custom gene panels with optional stacking of up to two 1,000-gene panels. Compared to Xenium, Atera has four times the throughput, six times higher plex capacity for targeted assays, 3.6x higher plex, and 2–3x sensitivity for whole transcriptome assays.

10x has said it plans to make Atera available in the second half of this year, though it has begun taking orders for the Atera, which is list-priced at $495,000 and measures roughly 53” x 36” x 64” or (4.42 ft × 3 ft × 5.33 ft).

Acquired for $350M

Xenium In Situ was developed by 10x using technology from ReadCoor, a company that 10x acquired in 2020 for $350 million. In 2016, Harvard licensed patents covering the technology exclusively to ReadCoor, a company founded by George M. Church, PhD, of Harvard Medical School.

Church and Je Hyuk Lee, MD, PhD, founder of Terrain Life Science and an investigator who developed Fluorescent In Situ Sequencing while a research fellow in Church’s lab more than a decade ago, are listed as first and second investors on all four patents.

The analyte detection patents (‘737, ‘276, and ‘277) also list two other Church lab alumni: Daniel Levner, PhD, co-founder and CTO of Emulate; and Michael Super, PhD, senior director, translational R&D with the Hansjörg Wyss Institute for Biologically Inspired Engineering at Harvard University, as co-inventors.

The amplicon sequencing patent (‘358) lists as co-inventors two other Church lab alumni: Richard C. Terry, who became ReadCoor’s CEO before his current post as CEO, CTO, and founder of cell therapy manufacturer Harton, and Evan R. Daugharthy, PhD, Harton’s president, CSO, and founder.

The post 10x Genomics, Harvard Target Element’s Multiomics Platform in Patent Lawsuit appeared first on GEN – Genetic Engineering and Biotechnology News.

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Revolution’s aftermath: population based cross-sectional study to understand the intergeneration mental health and wellbeing following the 2024 student-led uprising

BackgroundBangladesh was confronted with a nationwide student uprising in July 2024, that exposed both participants and observers to widespread unrest and traumatic events. To better understand the kind of support the population will need, it is important to understand its immediate impact on mental wellbeing.AimAim was to examine the prevalence of trauma symptoms among the Bangladeshi general population, aged 15+, within three-months following revolution.MethodsThis cross-sectional survey using the Post Traumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5, five-point Likert scale), was combined with a one-off online workshop to sensitise this population on mental health, trauma, and resilience. Associations between sociodemographic factors and PCL-5 scores were examined with multiple linear regression (ANOVA/ANCOVA). Probable PTSD (PCL-5 ≥ 31) was assessed using log-binomial regression. We estimated Population Attributable Fractions (PAF), Absolute Risk Reduction (ARR) to estimate the proportion of high PTSD attributable to each exposure, and applied min–max normalisation of Likert scales for cross-item comparison.ResultsMore than half of the surveyed participants (n=207; mean age 27.6 ± 9.7 years; 72% Gen Z) had clinically suggestive PTSD. This was more common among women (53.7%), and respondents from Chattogram (57.4%) and Khulna (66.7%). Adjusted analyses suggested modestly higher prevalence among Millennials (PR 1.23, 95% CI 0.87-1.74). PAF estimates indicated small contributions from age groups (Millennials +6.5%, GenX/Boomers -3.6%), and gender (men -3.1%). Under hypothetical elimination of exposure, absolute PTSD reduction was greatest among Millennials. Symptom clusters varied: women, and older adults showed consistently higher scores, while Gen Z reported more negative thoughts/feelings.ConclusionThe study underscores the potential higher prevalence of probable PTSD following large-scale demonstrations and confrontations, and recommends targeted culturally appropriate mental health interventions. Further research involving a representative sample from the population and longitudinal data is recommended to monitor long-term psychological impacts in Bangladesh.
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Therapeutic Interventions Targeted at Problematic Use of Digital Technology: Systematic Review and Meta-Analysis of Evidence

Background: Problematic use of digital technology has increased across the world. Despite growing research, evidence on treatment effectiveness across digital behaviors remains fragmented. Objective: This study aimed to systematically evaluate and compare the effectiveness of therapeutic interventions targeted at problematic use of digital technology across various behavioral domains. Methods: A systematic review and meta-analysis was conducted in accordance with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines (PROSPERO: CRD420251052442). Electronic searches of PubMed, Scopus, and Embase (up to April 2025) were conducted. It identified 125 eligible studies, including 73 randomized controlled trials (RCTs), 32 non-RCTs, 14 pre-post studies, and 6 pilot studies. The interventions that were assessed in these studies included psychological therapies, digital or web-based programs, exercise-based interventions, pharmacological treatments, neuromodulation, parent-focused programs, virtual reality–based interventions, educational programs, and multicomponent approaches. Random-effects meta-analyses using standardized mean differences (SMDs) were performed. Results: For problematic internet use, psychological treatments showed a strong effect (effect size=−2.68; <.001). Digital interventions also showed significant benefit (effect size=−1.16; <.001). For smartphone addiction, psychological treatments (effect size=−1.49; <.001) and exercise-based programs (effect size=−3.07; =.001) showed significant improvement. For gaming disorder, psychological treatments showed improvement (effect size=−1.01; =.02), but results were mixed. There were limited studies to calculate pooled results for social media addiction, pornography use, gambling, screen time, and over-the-top content watching. No treatment studies were found for problematic over-the-top content watching. High heterogeneity and evidence of small-study effects were observed in several studies. Conclusions: Overall, structured psychological therapies showed the most consistent benefit. These findings support structured interventions that aim for control of use and reduce cues linked to high use. Evidence remains limited for several emerging digital behaviors. More high-quality studies are needed in clinical settings and for less-studied forms of digital addiction.
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The Child Mind Institute Hosts 2026 Spring Luncheon “Future-Proofing Your Kids: Empowered Parenting in the Digital Age”

New York Times bestselling author Lisa Damour, PhD, led a thoughtful discussion to honor Mental Health Awareness Month

New York, NY – The Child Mind Institute, the leading independent nonprofit dedicated to transforming the lives of children struggling with mental health and learning disorders, hosted its 2026 Spring Luncheon on Monday, May 11. The event featured a dynamic discussion between Lisa Damour, PhD, a three-time New York Times bestselling author and host of the podcast, Ask Lisa: The Psychology of Raising Tweens & Teens, and Dave Anderson, PhD, Vice President of Public Engagement and Education and a senior psychologist at the Child Mind Institute. Their conversation was moderated by Ali Wentworth, an actress, comedian, author, and host of the television show, The Parent Test.

The event brought together advocates and distinguished individuals dedicated to equipping children and families with the skills they need to thrive in today’s rapidly evolving online and social environments. Attendees included Carson and Siri Daly, Jeannie Gaffigan, Kyle MacLachlan, Zibby Owens, and Alysia Reiner.

“We are raising children in a world fundamentally different from any generation before them…a world where childhood unfolds not just in homes and schools but online,” said Harold S. Koplewicz, MD, founding president and medical director of the Child Mind Institute. “Technology brings creativity and connection but also real risks: constant comparison, disrupted sleep, compulsive engagement, and exposure to harmful content. Our job is to help kids build the skills to navigate this world with resilience, confidence, and balance.”

The discussion centered on kids and families and how they can build healthy habits and resilience as they face the demands and distractions of a world increasingly reliant upon and centered around digital technology.

“My umbrella concern is what the conversation about technology is doing to the relationship between adults and kids. The single most powerful force for youth mental health is strong relationships with caring adults,” said Dr. Damour.

“If we focus on driving causal factors — such as family relationships, academic success, in-person friendships, sleep, and movement — we end up promoting a child’s wellness far more than by taking technology away,” said Dr. Anderson.

The luncheon raised over $260,000 to support the Child Mind Institute’s mission to change the lives of children with mental health and learning disorders in the United States and around the world.

The luncheon was co-chaired by Chris Mack, Lisa and Guy Metcalfe, Zibby Owens, and Jil Schaps. The host committee included Robyn and Paul Goldschmid, Desiree Gruber, Molly Jong-Fast, Breanna and John Khoury, Isabelle Krishana, Arielle Tepper, and Sarah J. Wetenhall.

Photos from the luncheon can be found here.

This special event is part of the Child Mind Institute’s programming during Mental Health Awareness Month. The Child Mind Institute recently launched its latest campaign, Mental Health Fitness. Physical fitness doesn’t just happen — it takes skills, regular practice, and a supportive environment. The same is true for mental health. Alongside relatable content from influencers and world-renowned athletes, the Mental Health Fitness resources from the Child Mind Institute provide kids and families with five core mental health skills they can practice every day.

About the Child Mind Institute 

The Child Mind Institute is dedicated to transforming the lives of children and families struggling with mental health and learning disorders by giving them the help they need. We’ve become the leading independent nonprofit in children’s mental health by providing gold-standard, evidence-based care, delivering educational resources to millions of families each year, training educators in underserved communities, and developing tomorrow’s breakthrough treatments. 

Visit Child Mind Institute on social media: Instagram, Facebook, X, LinkedIn

For press questions, contact our press team at childmindinstitute@ssmandl.com or our media officer at mediaoffice@childmind.org. 

The post The Child Mind Institute Hosts 2026 Spring Luncheon “Future-Proofing Your Kids: Empowered Parenting in the Digital Age” appeared first on Child Mind Institute.

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Brain Histamine Map Links Genetic Factors to Mental Health and Psychiatric Disorders

A study headed by researchers at King’s College London and the University of Porto has mapped the histamine system in the brain. Histamine, a molecule more commonly associated with allergies, plays a separate but poorly understood role in brain function. The new study addresses this gap, building the first multiscale map of the histamine system which spans from genetics to behavior and related mental health conditions.

The findings provide a new framework for understanding how this often-overlooked chemical system contributes to brain function and could point towards new treatment strategies for histamine-related conditions such as depression, ADHD, and schizophrenia. The study was funded by the National institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre.

Daniel Martins, MD, PhD, visiting senior research fellow at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King’s College London, said, “This work provides a crucial foundation for future research. By integrating molecular biology, brain imaging, and computational analysis, it offers a new perspective on how neurotransmitter systems are organized across the human brain. As neuroscience moves toward more integrated and personalized models of mental health, understanding systems like histamine may prove essential for unlocking new approaches to diagnosis and treatment.”

Martins is first and corresponding author of the team’s published paper in Nature Mental Health, which is titled “Mapping histamine pathway networks in the human brain across cognition and psychiatric disorders.” In their paper the team concluded, “This study provides an integrated characterization of the histaminergic system in the human brain, leveraging transcriptomic, neuroimaging, and functional datasets to delineate its molecular organization and relevance to brain function underlying cognition and psychiatric disorders.”

Histamine is a neurotransmitter, a molecule crucial for neurons to communicate with one another, the authors explained. “Neuronal histamine plays a crucial role in the regulation of brain function, serving as a neuromodulator with widespread influence across multiple neurotransmitter systems.” However, neuroscience research has classically focused on understanding other neurotransmitter systems such as dopamine and serotonin.

As the investigators noted, the organization of histamine in the human brain remains incompletely characterized. However, they explained, dysregulation of the histaminergic system has been implicated in a number of neuropsychiatric conditions, including anxiety, depression, schizophrenia, and autism spectrum disorder (ASD), as well as neurodegenerative diseases including Alzheimer’s, Parkinson’s, and Huntington’s diseases. “Therefore, targeting the brain histamine system has garnered significant attention as a potential new therapeutic strategy for treating these disorders, with pharmacological interventions aimed at modulating histamine receptor activity showing promise in preclinical models.”

Histamine acts through four known histamine receptors, which are responsible for how the signal will influence receiver neurons. Each of these histamine receptors, (histamine receptor H1 (encoded by HRH1), H2 (HRH2), H3  (HRH3) and H4 (HRH4)), mediates distinct functions. For their newly reported study, Martins and colleagues carried out what they described as multimodal analysis, integrating transcriptomic, neuroimaging, developmental and functional datasets to map the architecture of the histaminergic system.

To build a comprehensive map of how histamine acts in the brain, researchers first combined genetic and molecular data with physical maps of the brain.

This revealed which brain regions receive more input from the brain’s histamine system, and which parts show greater capacity to respond to histamine. These molecular data were then linked with positron emission tomography imaging of histamine receptors in living individuals, as well as functional neuroimaging databases that map brain regions to specific cognitive processes and mental health conditions. This type of scan shows how different parts of the brain are working by tracking a tiny amount of radioactive tracer in real time.

Their results found that different histamine receptors were found on brain cells that either turn activity up (excitation) or turn it down (inhibition). “The findings reveal that histaminergic genes exhibit distinct cellular and regional expression profiles, closely aligning with known histaminergic neuroanatomy and function,” they wrote. “At the single-cell level, histamine receptor H1 and histamine receptor H2 were enriched in excitatory neurons, whereas histamine receptor H3 showed preferential expression in inhibitory populations.” This suggests histamine may be important in maintaining the balance between excitation and inhibition, a fundamental property of healthy brain function.

Brain regions with higher histamine-related gene expression were consistently associated with processes such as emotional regulation, stress and fear responses, decision-making, impulsivity, reward, sleep, and memory.

The parts of the brain where histamine-related genes were most active also overlapped significantly with brain regions known to be affected in several psychiatric conditions, including attention-deficit/hyperactivity disorder, major depressive disorder, schizophrenia, and anorexia nervosa. This is in keeping with previous hypotheses linking histamine to these disorders. “By linking histaminergic gene expression to brain-cell types, neurotransmitter systems, cognitive domains and psychiatric disorders, these correlational findings generate several hypotheses concerning histamine’s critical role in brain organization, neurodevelopment and mental health, which further experimental mechanistic work should prioritize and build onto investigate causal relationships,” the investigators concluded.

Martins said, “Current psychiatric treatments largely target neurotransmitters such as serotonin and dopamine, yet histamine interacts closely with these systems and influences their activity. By providing a detailed map of histamine-related pathways, this work suggests new opportunities for developing treatments that target this system more directly, particularly for symptoms such as cognitive dysfunction, fatigue, and impaired motivation.

While these findings do not establish a direct causal role, they suggest that histamine signalling may contribute to regional vulnerability in these disorders. This aligns with a growing view in psychiatry that mental health conditions arise from disruptions across interacting brain systems rather than a single chemical imbalance.”

This new map paints a neural picture of a previously lesser-studied molecule. It opens up future avenues of research into exactly what histamine is doing in various cell types and parts of the brain.

“We want to emphasise that these findings are hypothesis-generating and based on large-scale datasets that capture patterns rather than direct mechanisms,” commented senior author Steve Williams, PhD, professor of neuroimaging at IoPPN King’s College London. Future studies will focus on testing how histamine signaling changes in living individuals, for example through pharmacological interventions or longitudinal imaging approaches.

Co-author Daniel Van Wamelen, PhD, clinical senior lecturer in neuroscience at IoPPN, King’s College London and one of the authors on the paper said: “This kind of work is already taking place at King’s College London, for example in the iMarkHD project. In this project we use Positron Emission Tomography scans to study a specific histamine receptor (called H3) in people with Huntington’s disease, an inherited condition that affects the brain. The goal is to see how histamine activity changes in different parts of the brain over time, and how these changes relate to symptoms such as apathy, depression, and anxiety.”

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Acute Myeloid Leukemia Therapy Improved by CRISPR Stem Cell Transplant

For highly aggressive types of blood cancer, stem cell transplantation is often the only potentially curative therapy. Yet, these cancers can often return even after a transplant. Notably, CAR T cell therapy has not been effective against all blood cancers, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).

A recent Phase I/II multicenter clinical trial, led by researchers at Washington University School of Medicine in St. Louis, shows that a stem cell transplant, that removes CD33 from donor cells using CRISPR, can help prevent cancer recurrence.

The work was published in Nature Medicine and titled, “CRISPR−Cas9 CD33-deleted allogeneic hematopoietic cell transplantation with gemtuzumab ozogamicin maintenance in AML: a Phase I/II trial.” The study was conducted at Siteman Cancer Center, based at Barnes-Jewish Hospital and WashU Medicine, and 14 other sites in the U.S. and Canada. 30 adult patients with AML or MDS at high risk of relapse received the stem cell transplant.

Myeloid cancers, such as AML and MDS, are difficult to treat with CAR T cells because the same proteins targets are present on both cancer cells and healthy myeloid cells, leading to toxicity risks.

“We are encouraged by the results of this study showing that a CD33-deleted stem cell transplant looks very similar to the outcomes of standard stem cell transplantation,” said John DiPersio, MD, PhD, professor of medicine at WashU Medicine and corresponding author of the study. “In the future, we are hopeful we will be able to combine this with CD33-targeted immunotherapies, such as CAR T cells, and improve treatment options for patients with these very aggressive blood cancers.”

As proof of concept, patients also received a maintenance therapy that targets CD33, after completion of the stem cell transplant. While not a CD33-targeted CAR T cell, the maintenance therapy, called gemtuzumab ozogamicin, is an engineered antibody that targets CD33 and carries an anti-cancer drug. Gemtuzumab ozogamicin is approved by the Food and Drug Administration (FDA) to treat CD33-positive AML and is in clinical trials for CD33-positive MDS. While it helps prevent relapse, the drug’s use is limited because it can cause liver toxicity and damage to blood cells, including dangerously low counts of white blood cells, red blood cells, and platelets.

All patients from the trial achieved engraftment of their transplanted stem cells by day 28. Some patients met this goal sooner with platelet production returning by day 16 on average. These timeframes are comparable to those of standard transplanted stem cells.

Average survival was just over 14 months. Nineteen patients received at least one cycle of the antibody maintenance therapy as part of a dose-escalation protocol. The authors found that patients maintained blood cell counts across all doses, suggesting that the gene-edited stem cell transplant protected patients from low blood cell counts typically seen following a standard stem cell transplant.

DiPersio and colleagues published a single case study detailing a patient with high-risk AML who received a CD33-deleted stem cell transplant. Upon relapse after the transplant, the patient received a CD33-targeted CAR T cell therapy, which used T cells from the same donor who provided the stem cell transplant.

The treatment resulted in complete remission and the patient remains cancer free over one year after receiving the CAR T cell therapy. Normal blood cell production returned with all blood cells lacking CD33, providing evidence that the genetically engineered donor cells had established themselves in the bone marrow.

DiPersio said the results of the study lay the groundwork for developing paired CD33-deleted stem cell transplant and CD33-targeted immunotherapy interventions that avoid destruction of healthy donor cells in the course of cancer treatment.

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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.