ObjectiveThis study aimed to develop and evaluate a culturally adapted psychoeducational intervention to address the severe psychological distress and caregiving burden commonly experienced by caregivers of newly diagnosed pediatric hematologic malignancy patients during the early stages of illness.MethodsAmong 116 randomized caregivers, 90 completed all three assessments and were included in the complete-case analysis. The intervention group received a 4-week psychoeducation program delivered by medical social workers, whereas the control group received routine care. Outcomes were assessed at baseline, post-intervention, and 48-day follow-up.ResultsCompared with controls, caregivers in the intervention group showed greater reductions in depressive and post-traumatic stress symptoms after the intervention, and these reductions were maintained at follow-up. Caregiver burden showed a delayed reduction, with between-group differences becoming apparent at follow-up. Anxiety levels decreased over time in both groups, but the group × time interaction was not statistically significant.ConclusionThe culturally adapted psychoeducational intervention was associated with reductions in depressive and post-traumatic stress symptoms and a delayed reduction in caregiver burden, but did not show an additional effect on anxiety beyond routine care. These findings provide preliminary support for structured, culturally responsive psychoeducational support in pediatric hematology settings.
Clinical correlates and cognitive associations of the neutrophil-to-lymphocyte ratio in first-episode psychosis and at-risk mental states
ObjectiveClinical high-risk for psychosis (CHR-P) and first-episode psychosis (FEP) individuals present immune alterations that precede treatment initiation. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a simple, accessible marker of systemic inflammation. This study investigates differences across CHR-P, FEP, and healthy control (HC) populations and explores peripheral associations between NLR and demographic, clinical, and cognitive variables.MethodsData were collected from 63 FEP, 56 CHR-P, and 27 HC individuals from two early intervention services in Spain. Socio-demographic, clinical, and neurocognitive data were collected from all participants, along with peripheral blood samples for NLR calculation. Correlations between NLR and clinical and neurocognitive variables were analyzed using multivariate models to control for potential confounders.ResultsNo significant differences in NLR were observed between the FEP, CHR-P, and HC groups (F = 1.04; p=0.36). In the FEP population, NLR was positively correlated with higher levels of positive symptoms (β=0.035; p=0.01) and longer duration of untreated psychosis (β=0.003; p=0.04) after adjusting for sex and age. In CHR-P individuals, NLR was negatively correlated with antidepressant use (β=-0.664; p=0.02). No significant associations were found between NLR and neurocognitive performance or antipsychotic treatment in any clinical group.ConclusionsOur findings do not support the utility of NLR as a diagnostic biomarker in early psychosis. However, the observed association between elevated NLR and positive psychotic symptoms in FEP suggests that NLR could serve as a state biomarker, reflecting inflammatory status related to symptom severity. Further research is needed to explore NLR dynamics in larger samples and its potential role in monitoring clinical progression in psychosis.
Senior NIH scientist, research fellow charged with bringing deactivated mpox virus into U.S.
DETROIT — Two scientists at a U.S. government lab were charged with smuggling vials of deactivated mpox virus into the country from Africa and lying about it during interviews with investigators at a Michigan airport, authorities said Tuesday.
A criminal complaint was unsealed in federal court in Detroit against Vincent Munster, who is chief of the virus ecology section at Rocky Mountain Laboratories in Hamilton, Montana, and Claude Kwe, who works with him as a research fellow.
Tics and OCD: Why Treatments Differ and Ways to Support Your Kids
by Dr. Christine Conelea and Dr. Adrienne Manbeck
Tics, compulsions, and obsessions are part of many people’s everyday lives. As clinicians and researchers at the University of Minnesota Tic and Compulsivity Lab (MnTiC), we see people living with different, unique combinations of these symptoms that can feel interconnected. There are some broad differences between tics, obsessions, and compulsions, but it’s important to note that they do overlap and that a person can have all of these things at the same time. Still, disentangling symptoms in order to provide effective treatment can sometimes be challenging.
Tics and compulsions are similar in that they both involve movements that are repetitive and difficult for the person to control. Research has shown that overlapping genetic, neurological, and psychological factors contribute to both experiences. Because of this, researchers and clinicians consider both tics and compulsions to be on the “obsessive-compulsive spectrum.” However, there are important differences in treatment and in how loved ones can provide support.
Behaviors
Tics are sudden, repetitive, involuntary movements or sounds that are usually very brief. Common tics include rapid or hard eye blinking, facial scrunching, throat clearing or sniffing. In our studies, we have found that people with tics have an average of 8 tics per minute.
Many individuals with tics experience an urge right before they tic. This urge can feel like tension, an itch or pressure that typically goes away after the tic occurs. Tics tend to wax and wane over time. Compulsions are often more rule bound or rigid and are driven by a thought. Common compulsions include checking, counting, washing and reordering. They tend to be longer, smooth movements or sequences of movements. They’re linked to very specific situations, triggers, or thoughts to prevent something bad from happening or to relieve anxiety.
Why Treatments Differ
Although tic disorders and OCD sometimes look similar on the surface (repetitive movements can occur in both), they are different disorders. Subjectively speaking, tics can feel like a “body itch” while compulsions might feel like a “brain itch.” Though they may be very connected for some people, what works for one won’t necessarily work for the other.
In general, we often take a less interventionist approach to tic disorders because tics may not be inherently harmful. On the other hand, because compulsions work to reinforce obsessive thoughts and provide escape from non-harmful but unpleasant feelings, we often intervene with OCD as soon as possible. As clinicians working with children and teens, we want to help kids learn to be brave, learn that they can tolerate distress associated with anxiety, and learn that OCD doesn’t get to make their decisions for them.
Watchful Waiting
In general, OCD will not get better on its own. If a parent notices symptoms associated with distress or impairment, taking action of some kind is often the best approach. If tics aren’t causing problems for a child, it might be best to monitor. If tics become painful, start to bother your child, or in some other way cause harm, that might be the time to pursue treatment. The American Academy of Neurology refers to this as “watchful waiting” and sees it as an appropriate treatment, in some cases, for tics.
Tips for Providing Support
People with tic disorders face high stigma and discrimination compared to the general population. Tics are often hyper-visible and poorly understood. For OCD, stigma is more likely to emerge from public messaging rather than hypervisibility. The general public talks about OCD in a highly stereotyped way that misses a lot of people’s actual experiences with OCD and can trivialize symptoms.
For both OCD and tic disorders, parents can help support their child by collaboratively developing a reward structure for hard work in therapy.
For tic disorders, research has shown that situational factors have an important role in influencing tics, including what a person is doing, who is around them, and how they are feeling. Most people can identify situational factors that make their tics better or worse. Some factors frequently associated with tic exacerbation are fatigue, social events, and starting school in the fall. Stress, frustration, or anxiety-provoking events can make it harder for the brain to inhibit tics. Events frequently reported to coincide with tic reductions include social interactions with familiar people, situations in which the individual is a passive participant or deeply focused on a task, and leisure activities.
Because tics are so reactive to situational factors, one of the best ways to provide support is to create tic-neutral environments. This means eliminating intended or unintended consequences related to the tics, such as minimizing reactions to tics or changes to activities because of tics. We frame this as, “focusing on the person instead of the tics.” Tic neutrality can also help children feel better about tics since they can’t control them.
For OCD, minimizing parent accommodation, parents helping kids avoid anxiety-provoking things, can be helpful. Parents can help their kids by reducing accomodation and encouraging their children to be brave and face their fears in manageable, developmentally-appropriate ways.
About the Authors:
Christine Conelea, PhD is an Associate Professor in the Department of Psychiatry & Behavioral Sciences at the University of Minnesota, a licensed clinical psychologist, and the director of the MnTiC Lab. Dr. Conelea’s research interests include Tourette Syndrome/tic disorders, obsessive-compulsive disorder (OCD), and anxiety disorders. She is particularly interested in understanding how the brain, environment, and psychosocial factors interact to impact symptoms and treatment outcomes.
Adrienne Manbeck, PhD, is a postdoctoral fellow in the MnTiC Lab. Dr. Manbeck earned her doctorate in clinical psychology at the University of Minnesota and completed her pre-doctoral internship at Allegheny General Hospital in Pittsburgh, PA. Dr. Manbeck’s research aims to better understand the development, maintenance, and treatment of OCD and anxiety disorders across the lifespan, with a particular emphasis on the impact of societal stressors on these disorders, including the ways in which societal stressors impact symptom severity, access to high-quality treatment, and impact of treatment on symptoms.
More Reading:
Micali, N., Heyman, I., Perez, M., Hilton, K., Nakatani, E., Turner, C., & Mataix-Cols, D. (2010). Long-term outcomes of obsessive–compulsive disorder: Follow-up of 142 children and adolescents. British Journal of Psychiatry, 197(2), 128–134.
Conelea, C.A., Woods, D.W., Zinner, S.H. et al. The Impact of Tourette Syndrome in Adults: Results from the Tourette Syndrome Impact Survey. Community Ment Health J 49, 110–120 (2013).
Tourette Association of America Tourette Awareness Month resources
MnTiC Lab
Check out our research
Stay in touch! Subscribe to our newsletter
The post Tics and OCD: Why Treatments Differ and Ways to Support Your Kids appeared first on International OCD Foundation.
Eye-Tracking Technologies for Cognitive Assessment After Acquired Brain Injury: Systematic Review
Background: Acquired brain injury (ABI) is a heterogeneous umbrella term encompassing traumatic and nontraumatic etiologies and is frequently associated with persistent cognitive dysfunction. Conventional neuropsychological assessment remains central to clinical evaluation, but feasibility and measurement precision may be limited in individuals with motor impairment, aphasia, reduced stamina, or fluctuating arousal. Eye tracking offers an objective, low-burden approach that can quantify gaze behavior during task engagement and may provide complementary process-level markers of cognition. Objective: This study aimed to systematically synthesize the evidence on eye-tracking paradigms used as a primary approach for cognitive assessment in ABI and to summarize findings by cognitive domain, paradigm, and clinical interpretability. Methods: We conducted a PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020–compliant systematic review and registered the protocol in PROSPERO (CRD420251038768). PubMed, Web of Science, the Cochrane Library, Embase, EBSCOhost, PsycINFO, and Scopus were searched from inception to April 10, 2025. We included peer-reviewed English-language studies enrolling children or adults with ABI in which eye tracking was the primary assessment modality used to quantify at least one cognitive domain or clinically relevant cognitive-communication process. Two reviewers independently screened studies, extracted data, and assessed methodological quality using design-appropriate tools (Risk of Bias 2, Risk of Bias in Non-Randomized Studies of Interventions, Quality Assessment of Diagnostic Accuracy Studies 2, and the Newcastle-Ottawa Scale). A structured narrative synthesis was performed because of heterogeneity in paradigms and outcome definitions. Results: Twenty-seven studies met the inclusion criteria (N=872 participants; females: n=354 and males: n=518), with most evidence derived from mild traumatic brain injury cohorts, and fewer studies involving stroke, mixed etiologies, and disorders of consciousness. Across domains, antisaccade and related paradigms were commonly associated with differences in inhibitory control and executive function, while predictive tracking, smooth pursuit, and target-blanking paradigms frequently captured alterations in attentional prediction and timing. Virtual reality (VR) free-viewing paradigms identified visuospatial exploration asymmetries in stroke-related neglect, and gaze-based human-computer interface approaches demonstrated above-chance task performance in a subset of patients with disorders of consciousness. Evidence for incremental validity beyond conventional assessment was mixed and often indirect, and safety reporting was uncommon. Overall certainty of evidence was generally low and limited by small sample sizes, cross-sectional designs, and heterogeneity in acquisition procedures, metrics, and analytic pipelines. Conclusions: Eye tracking shows potential as an adjunctive, process-level approach for quantifying specific cognition-relevant behaviors after ABI, particularly within paradigms targeting inhibitory control and predictive attention. Current evidence is insufficient to support broad diagnostic claims or the routine replacement of conventional neuropsychological assessment. Future research should prioritize harmonized paradigms and reporting standards, external validation of classification models, longitudinal designs, and explicit feasibility and safety reporting to clarify when eye tracking provides incremental clinical value for precision neurorehabilitation.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/a683e26d5f5b1f17e940b9e6925b9106" />
Surveillance of Cannabis Strains Using Online Data: Observational Study
Background: The flower strains of cannabis are an important attribute that determines product appeal and health impacts. However, there is a lack of surveillance of cannabis strains as the marketplace expands in response to the growing legalization of recreational and medical cannabis. Objective: This study aimed to analyze cannabis strains and their growth using existing data from user-generated reviews on the Leafly website. Methods: Using the time stamps of each review, we constructed a dataset of the number of reviews by strain and year over the period of 2010 to 2023. We further conducted trend analyses using Joinpoint regression. Results: As of December 2023, more than 7000 cannabis strains are available for view or purchase on the website, including more than 6000 that have been reviewed by users or customers. The number of strains with reviews experienced a 13-fold increase from 280 strains in 2010 to 3905 strains in 2023. Strains that are hybrid and contain more than 20% tetrahydrocannabinol experienced the highest growth in review numbers. Conclusions: The rapid growth of strain numbers poses challenges to cannabis regulation. Policymakers who would like to base regulations on product features need to consider the variability of strains, along with other features such as potency levels and product forms.
<img src="https://jmir-production.s3.us-east-2.amazonaws.com/thumbs/0a0eb0fa61181f1ac8ac90d4cc83810b" />
Cross-Reactive T Cells Could Point to Broad Vaccines or Treatments for Measles, Nipah Virus
T cells are some of the immune system’s most important fighters. They can stop tumor growth and fight off severe infections. Scientists at La Jolla Institute for Immunology (LJI) have now reported a study indicating how T cells target paramyxoviruses, a viral family that includes measles virus and Nipah virus.
Paramyxoviruses are pathogens of pandemic concern. Measles virus is highly infectious, and Nipah virus has a high mortality rate. The new study shows how we might harness T cells to save lives. Headed by Alessandro Sette, PhD, the team systematically mapped human CD4+ T cell epitopes across Nipah and measles viruses, and analyzed T cells from donors who had previously received the MMR vaccine that protects against measles, and another paramyxovirus, mumps (as well as rubella), and who had not been exposed to Nipah virus. Their experiments showed that the two paramyxoviruses had conserved T cell epitopes (CTERs) in common, and that cross-reactive T cells can recognize multiple paramyxovirus species at once.
Instead of vaccinating against one virus at a time, the researchers found that activating these cross-reactive T cells may protect against the wider paramyxovirus family. This broad protection is essential when you don’t know which virus will strike next.
The discovery may guide the development of new vaccines and therapies that stop measles, Nipah, and other paramyxovirus infections before they turn deadly. “No one knows which particular viral species or strain of a virus might be responsible for an outbreak, as we’ve seen in the recent cases of Andes hantavirus,” Sette said.
Sette and colleagues reported on their findings in Cell Reports Medicine, in a paper titled “Comprehensive mapping of human CD4+ T cell epitopes for Nipah and measles as prototype Paramyxoviruses,” concluding, “Collectively, these findings support the concept that CTER-based immunogen design can both broaden protective coverage and strategically harness existing population immunity while complementing neutralizing antibody-based vaccine approaches.”
![LJI Professor Alessandro Sette, Dr.Biol.Sci. [La Jolla Institute for Immunology]](https://www.genengnews.com/wp-content/uploads/2026/06/Low-Res_Alessandro-Sette-233x300.jpg)
The Paramyxoviridae family, which includes measles and Nipah viruses, represents “… a plethora of viruses that impact global human health,” the authors wrote. “Understanding adaptive immune responses to these viruses is critical for characterizing host-pathogen interactions and evaluating vaccine performance.”
A part of the adaptive immune system T cells learn to target a specific threat. A T cell might respond to influenza virus infection but not malaria parasite infection. To do this T cells recognize specific epitopes on the pathogen. In general, T cell epitopes on one pathogen look very different from T cell epitopes on another pathogen.
![LJI Research Assistant Professor Alba Grifoni, Ph.D. [La Jolla Institute for Immunology]](https://www.genengnews.com/wp-content/uploads/2026/06/Low-Res_2024-05-Picture-Day-Alba-Grifoni-3-200x300.jpg)
But viruses may retain some “conserved” features that remain unchanged within viral families. LJI scientists have shown that some T cells can cross-react to different viruses, as long as the viruses share similar epitopes. In a series of landmark studies during the COVID-19 pandemic, Sette, LJI research assistant professor Alba Grifoni, PhD, LJI assistant professor Daniela Weiskopf, PhD, and professor and chief scientific officer Shane Crotty, PhD, showed that cross-reactive T cells can recognize the family resemblance between different coronaviruses. A person who had previously contracted a common cold coronavirus may already have T cells primed to recognize SARS-CoV-2, the coronavirus that causes COVID-19.
More recently, Sette and Grifoni demonstrated that cross-reactive T cells may offer broad protection against the deadly Lassa virus and the wider viral family of arenaviruses. Their findings suggested that future vaccines and therapies could activate these cross-reactive T cells to protect against many dangerous viruses at once. Each study makes it clear that cross-reactive T cells are key to stopping emerging viruses.
Measles is a threat worldwide, and while an effective vaccine is available, the authors cited figures indicating that there were over 10 million estimated infections worldwide in 2023. “Measles remains one of the main causes of morbidity and mortality in children, due to secondary infections from measles-induced immune suppression,” they noted. People in Southeast Asia also have to keep watch for a related paramyxovirus threat, Nipah virus, which is spread by bats. Cases are rare but can be deadly. “Nipah virus is another Paramyxovirus of concern due to high mortality rates, often mediated by fatal encephalitis,” the investigators wrote. Nipah virus has a fatality rate of 40-75%, which is much higher than measles. “Outbreaks are becoming more and more frequent, especially in the Malaysian region,” said Grifoni.
The new LJI study suggests cross-reactive T cells may be just the weapons we need to combat the dangerous paramyxovirus family. The scientists worked with LJI’s John and Susan Major Center for Clinical Investigation to collect and analyze T cells from the blood of 31 study participants. These study participants had received their MMR vaccines, which protect against severe infection from the measles and mumps viruses (both are paramyxoviruses) and the rubella virus. As a result, the blood samples contained T cells that were ready to fight measles infection.
LJI postdoctoral fellow Alison Tarke, PhD, and LJI senior staff scientist Ricardo Da Silva Antunes, PhD, led experiments to map the T cell epitopes on measles virus. These findings were important on their own. “Even though measles has been studied for quite some time, and there is a vaccine for measles, there was not a lot known about the specific T-cell response elicited by the measles vaccine,” Sette commented.
Tarke and the LJI team then tested how these same T cells reacted to Nipah virus. From blood tests, the scientists knew that the study participants had never been infected with Nipah virus, yet they found that measles-fighting T cells could cross-react and also recognize Nipah virus. The two paramyxoviruses had conserved T cell epitope regions (CTERs) in common. “Focusing immune responses on these conserved regions could have a broad, protective capacity for the whole viral family,” says Sette. The authors added,
The new study is the first to map T cell epitopes on Nipah virus. The researchers were able to zero in on a specific epitope shared between measles and Nipah viruses: a region of the viral fusion or “F” protein. A large number of cross-reactive T cells targeted this relatively small, conserved viral structure. “It appears that if someone is vaccinated against measles, their T cells will have some degree of cross-reactivity to Nipah,” said Sette. “That raises the possibility that during a Nipah outbreak, one could perhaps vaccinate people with a measles vaccine, and this cross-reactivity could potentially offer some benefit.”
The authors further noted, “In light of these findings, current Nipah vaccine candidates, many of which focus primarily on whole-protein antigens selected to maximize neutralizing antibody responses, particularly F and G glycoproteins, could potentially be optimized by incorporating conserved T cell epitope regions.” Added Grifoni, “Activating T cells can be your first line of defense when you don’t know what’s going to be thrown at you.”
In their paper the team concluded “With specific regard to vaccine strategies targeting Nipah or other paramyxoviruses, one anticipated outcome of focusing on CTERs, particularly those shared with measles and mumps viruses, is the potential to boost preexisting cross-reactive memory T cell responses in populations where MMR vaccination is widespread.”
The post Cross-Reactive T Cells Could Point to Broad Vaccines or Treatments for Measles, Nipah Virus appeared first on GEN – Genetic Engineering and Biotechnology News.
Fulcrum Halts Development of SCD Candidate Pociredir, Sets Strategic Review
Fulcrum Therapeutics said today it is scrapping its lead pipeline program to develop pociredir as a treatment for sickle cell disease (SCD) and launching a “comprehensive” review of strategic alternatives, after the FDA told the company it had heightened concerns about the drug’s risks and benefits in fighting the disease.
Those concerns, which the agency raised with Fulcrum executives at a recent end-of-phase meeting, stemmed from an unexpectedly high rate of secondary blood cancers seen with another PRC2 inhibitor—Ipsen’s Tazverik® (tazemetostat), indicated to treat follicular lymphoma and epithelioid sarcoma, the company disclosed, based on meeting minutes received May 28.
Ipsen voluntarily withdrew Tazverik from the market in March following adverse events of secondary blood cancers emerging from the ongoing Phase Ib/III SYMPHONY-1 trial (NCT04224493), which evaluated the drug in combination with lenalidomide plus rituximab (R2) vs R2 in follicular lymphoma. Ipsen inherited the drug when it acquired its developer Epizyme in 2022 for $247 million. Tazverik last year generated €40.6 million ($47.2 million) for Ipsen and another $2.5 million for Hutchmed, which marketed the drug in China. The withdrawal also affected Eisai, since it marketed Tazverik in Japan and manufactured the drug there.
Pociredir is an oral small molecule polycomb repressive complex 2 (PRC2) inhibitor targeting embryonic ectoderm development (EED), and was discovered using Fulcrum’s discovery technology. Fulcrum has reasoned that inhibiting EED leads to potent downregulation of key fetal globin repressors including BCL11A, thereby causing an increase in fetal hemoglobin (HbF).
“Fulcrum submitted information to FDA supporting the position that mechanistic differences between EED (pociredir’s target) and EZH2 (tazemetostat’s target), which perform different biological roles, were relevant to the benefit-risk assessment,” Fulcrum said in a statement. “While no new safety signals have been observed to date with pociredir, the FDA raised concerns regarding the potential malignancy risk associated with pociredir’s inhibition of the PRC2 complex.
The agency considered Fulcrum’s position before rebuffing the company, concluding that any drug intervention targeting the PRC2 complex carries equivalent malignancy risk “regardless of the specific subunit engaged,” Fulcrum continued, based on pociredir’s previously disclosed preclinical malignancy observations.
That left no viable regulatory path forward for further clinical development of pociredir, Fulcrum concluded.
No path forward
“Following a thorough review of regulatory feedback, the totality of available data, and the implications for a viable regulatory path, we have made the very difficult decision to discontinue development of pociredir,” stated Alex C. Sapir, Fulcrum’s president and CEO. “We arrived at this decision after discussion with the FDA, and despite robust elevations in fetal hemoglobin seen with pociredir and the potential for clinical benefit, we do not see a path forward with pociredir.”
“We know the SCD community has faced many disappointments and setbacks related to innovation for this devastating disease,” Sapir added. “We are not only humbled but forever grateful to the SCD warriors, investigators, and broader SCD community who have worked tirelessly alongside Fulcrum to evaluate new treatment options for this devastating disease.”
Pociredir is not the first SCD therapy to be scrapped. In 2024, Pfizer withdrew Oxbryta® (voxelotor) from the market, citing deaths and vaso-occlusive crises occurring in patients given Oxbryta in clinical studies. Hours before Pfizer’s announcement, the European Medicines Agency (EMA) disclosed findings from two Phase III trials of Oxbryta in which a total of 18 deaths occurred—all but two of them reported in patients who were dosed with the drug.
Pfizer inherited Oxbryta when it acquired the drug’s original developer, Global Blood Therapeutics (GBT), for $5.4 billion, a deal completed in 2022.
Vivien Sheehan, MD, PhD, director of Translational Sickle Cell Disease Research at Emory University School of Medicine, told GEN Fulcrum’s data was “reasonable, although not game changing.”
“I don’t take it [Fulcrum’s halt to pociredir development] as an abandonment of SCD,” said Sheehan, who is also a member of the Discovery and Developmental Therapeutics Research Program at Winship Cancer Institute of Emory University. “There may not have been a path forward, and more efficacious drugs in the pipeline may have also influenced the decision.”
She expressed greater enthusiasm for a potential SCD treatment being developed by Bristol Myers Squibb (BMS)—BMS-986470, an oral HbF-activating cereblon (CRBN) E3 ligase modulator (CELMoD
) agent designed as a potential first-in-class degrader of both transcription factors zinc finger and BTB domain containing 7A (ZBTB7A) and widely interspaced zinc finger (WIZ).
BMS-986470 is now under study in an ongoing Phase I/II trial (NCT06481306) designed to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics, pH and food effect, and preliminary efficacy of BMS-986470 in healthy volunteers and participants with SCD. The study’s estimated primary completion date is January 6, 2027, according to ClinicalTrials.gov.
A 2024 preclinical study by a team of BMS researchers showed BMS-986470 to have generated “robust γ -globin induction activity leading to HbF levels predicted to significantly ameliorate SCD pathology.”
$1.5B peak sales forecast
In ending development of pociredir, Fulcrum has scrapped a drug that stood to generate as much as $1.5 billion in projected peak sales by 2038, according to BofA Securities, which predicted a 2029 commercial launch for the drug.
Investors responded to Fulcrum’s halt to development of pociredir with a stock selloff that sent shares of Fulcrum on the Nasdaq Global Market plummeting 51% Tuesday, to $3.13 from yesterday’s closing price of $6.42.
As a result of scraping development of pociredir, Fulcrum said, it will explore potential strategic alternatives, “including, but not limited to, a merger, acquisition, business combination, or other strategic transactions involving the company or its assets.”
Fulcrum said it has also begun efforts to “significantly” reduce its operating expenses and preserve capital. Fulcrum finished the first quarter with $333.3 million in cash, cash equivalents, and marketable securities.
“We believe that our existing cash, cash equivalents, and marketable securities as of March 31, 2026 will enable us to fund our operating expenses and capital expenditure requirements into 2029,” Fulcrum stated in its Form 10-Q regulatory filing for the first quarter.
“With a strong balance sheet extending our cash runway into 2029, we are well positioned to advance pociredir through the next phase of clinical development,” Fulcrum stated in its April 27 press release.
The company has not set a timeline for completing its strategic review, adding that it does not intend to provide further updates “unless and until the board of directors has approved a course of action, the review process is concluded, or other disclosure is otherwise determined to be appropriate.”
Positive interim data
As late as April 27, when it held its quarterly earnings call with analysts to discuss first quarter results, Fulcrum had conveyed optimism about pociredir’s clinical prospects.
During the call, Sapir cited Fulcrum’s announcement of positive interim data from its Phase Ib PIONEER trial (NCT05169580) in February, which showed:
- A mean absolute HbF increase of 12.2% at 12 weeks of treatment with pociredir, rising from a baseline of 7.1% to 19.3%—what the company said represented “a rapid, robust, and clinically relevant response,” with progression toward pan-cellular HbF induction as F-cells increased from 31% to 63%.
- Absolute HbF levels ≥20% in 7 of 12 patients (58%), with all patients achieving at least a 6.5% absolute increase in HbF.
- Improvements in markers of hemolysis, improved erythropoiesis, and a >1 g/dL increase in total hemoglobin.
- Zero vaso-occlusive crises (VOCs) during the treatment period reported in seven of 12 patients (58%).
“Importantly, pociredir has continued to be generally well tolerated with no treatment-related serious adverse events reported to date,” Sapir told analysts. “Taken together, these data reinforce our conviction in pociredir’s potential to address the underlying biology of sickle cell disease—and support our belief that pociredir has the potential to represent a differentiated, once-daily oral treatment option for patients.”
The post Fulcrum Halts Development of SCD Candidate Pociredir, Sets Strategic Review appeared first on GEN – Genetic Engineering and Biotechnology News.
Disease Detection Gets Boost from Keck’s New Brain Reference Map
Investigators at the USC Mark and Mary Stevens Neuroimaging and Informatics Institute (Stevens INI) at the Keck School of Medicine say they have created one of the largest reference models ever developed for the human brain, using diffusion MRI scans from more than 54,000 people to chart how the brain’s communication pathways develop, mature, and decline across the lifespan.
Published in Nature Communications, the study “Lifespan normative modeling of brain microstructure” provides the equivalent of growth charts for the brain’s white matter, the vast network of neural wiring that allows brain regions to communicate, according to the Keck team, which adds that the novel tool offers researchers a new way to detect subtle patterns linked to aging, Alzheimer’s disease, schizophrenia risk, and other neurological and psychiatric conditions.
“Just as pediatric growth charts help clinicians determine whether a child’s height or weight is developing as expected, these brain charts provide a reference for how the brain’s neural pathways typically change over the lifespan,” said Julio E. Villalón-Reina, MD, PhD, a postdoctoral researcher at the Stevens INI and the study’s first author. “That gives us a powerful new way to identify when an individual’s brain wiring falls outside the expected range.”
To study white matter, the team used diffusion MRI, an imaging method that tracks how water moves through brain tissue. Because water movement is shaped by microscopic features such as nerve fibers and myelin, diffusion MRI can reveal subtle changes in tissue organization not visible on standard brain scans.
After compiling diffusion MRI data from 54,583 individuals across 19 international datasets, the researchers built statistical growth and decline charts for the brain’s neural pathways.
The researchers focused on four widely used measures of white matter microstructure across 21 major brain regions. By modeling how these measures vary by age and sex, they generated lifespan curves and percentile ranges that show what is typical at different stages of life.
![Statistical charts compiled from a large population allow brain abnormalities to be detected in new individuals. [Stevens INI]](https://www.genengnews.com/wp-content/uploads/2026/06/Julio-Villalon-press-release-image-1920x1080-1-1024x576.jpg)
The results revealed that white matter follows distinct developmental and aging trajectories, with some measures reaching peak maturity in early adulthood and others later in midlife.
“Brain development and brain aging are not uniform processes,” continued Villalón-Reina. “The brain’s neural pathways mature on distinct timelines, and some are more vulnerable to decline than others. Our model reveals this structure by merging data on a truly global scale.”
The scientists also discovered evidence for a longstanding theory of brain aging, sometimes described as last in, first out. According to this theory, brain pathways that develop last in childhood and adolescence tend to be more susceptible to decline in older age. The researchers observed that white matter regions that mature later did indeed decline faster in old age, offering new insight linking brain development and aging.
To demonstrate the model’s practical value, the researchers applied it to clinical datasets from people with mild cognitive impairment, dementia, and 22q11.2 deletion syndrome, a genetic condition that increases risk of schizophrenia.
In each case, the model identified alterations in the brain’s circuitry that deviated from age-expected norms. Importantly, these deviations were not identical across individuals with the same diagnosis, highlighting the value of a person-specific approach.
“This monumental study took seven years to complete,” explained Paul M. Thompson, PhD, associate director of the Stevens INI and senior author of the study. “The vast scale of the data and the fine scale of the brain features assessed means we can now evaluate your neural pathways relative to other people of the same age, sex, and demographics. We can see how your brain differs from what we would expect for a person of your age and sex, giving us a tool to use in clinical trials of treatments for dozens of brain diseases.”
When applied to people with dementia and mild cognitive impairment, the model detected atypical white matter patterns in brain regions involved in memory and interregional communication. In people with 22q11.2 deletion syndrome, it identified deviations in multiple key neural pathways, helping researchers discover which brain systems develop differently.
The reference charts may also help researchers evaluate treatments by tracking whether a person’s white matter measures move closer to the expected range, or whether a treatment slows the shift away from healthy patterns over time. The charts will now be used to compare more than 30 brain diseases and conditions, offering a common framework for studying how different disorders emerge, progress, and respond to intervention.
The models are also a publicly available resource that can be extended as additional brain imaging data become available. The methods are now being used to study neurological, psychiatric, and neurodevelopmental disorders by providing a common reference standard for white matter microstructure across the lifespan.
“This study demonstrates the power of large-scale, international data sharing to create tools the entire research community can use,” pointed out Arthur W. Toga, PhD, director of the Stevens INI and provost professor at USC. “By establishing a lifespan framework for the brain’s communication pathways, this work opens new opportunities to detect subtle disease-related changes, compare conditions more rigorously, and move toward a more individualized understanding of brain health.”
The post Disease Detection Gets Boost from Keck’s New Brain Reference Map appeared first on GEN – Genetic Engineering and Biotechnology News.
Mature Intestinal Cells Revert to Stem-Like State to Sustain Colorectal Cancer
Researchers at the Stevens Institute of Technology have identified a mechanism that helps explain how colorectal cancer (CRC) develops, persists, and resists treatment. The research, published in the journal Cell Death & Disease, shows that mature intestinal cells that revert to a stem cell-like state can sustain tumor growth more effectively than mutated intestinal stem cells, a finding that could inform new drug development strategies focused on preventing CRC recurrence.
“Our study suggests that intestinal cancers can arise not just from damaged stem cells, but also from cells that revert into stem-like cancer cells,” said senior author Ansu Perekatt, PhD, an assistant professor of chemistry and chemical biology at Stevens Institute of Technology, “and they may contribute to why colorectal cancer can be diverse and resistant to treatment.”
Colorectal cancer is the second leading cause of cancer-related death worldwide. Cancer stem cells are known to play a role in tumor growth, metastasis, treatment resistance, and relapse. The new study focused on understanding how these cancer-driving stem cell populations emerge within the intestinal epithelium.
Two different models have been proposed for how colorectal cancer can develop. The most widely held belief is the “bottom-up” model which suggests that mutations in stem cells initiate tumor formation. By comparison, the “top-down” model suggests that mature epithelial cells acquire mutations, dedifferentiate into stem-like cells, and then drive tumor growth. Histological features observed in many human colorectal tumors have suggested a luminal, or top-down, origin.
Under normal conditions, Lgr5-positive stem cells reside in intestinal crypts and their role is to replenish the intestinal lining. As their progeny migrate from the crypts toward the villi in the intestine walls, they stop dividing and become specialized mature cells. However, previous research has shown that the intestinal epithelium is highly plastic and that differentiated cells can regain stem cell characteristics under certain conditions.
To better understand the biology of these pathways, the Stevens employed mouse model carrying Smad4 loss-of-function and β-catenin gain-of-function mutations, to mimic two common drivers of human colorectal cancer. They then tracked the behavior of both stem cells and differentiated epithelial cells.
The researchers also performed single-cell RNA sequencing to characterize the cellular populations that emerged during tumor initiation and progression allowing them to compare mutant stem cells residing in the crypts with dedifferentiation-derived stem-like cells arising in the villi.
The data showed that mutant Lgr5-positive stem cells in the crypts were at a competitive disadvantage. While they carried cancer-associated mutations, many were displaced and ultimately replaced by normal stem cells. At the same time, a subset of progenitor and epithelial cells underwent dedifferentiation and reacquired stem-cell properties making them capable of sustaining tumor growth.
“We don’t know why they change and why only a subset changes,” Perekatt said. “It’s very random, very sporadic. But when they change, they develop tumors.”
According to the study, dedifferentiating epithelial cells showed early expression of both CD44 and Lgr5, markers associated with stemness and tumor initiation. The Stevens team also found abnormal activation of Notch signaling in villus epithelial cells before the formation of tumor-associated crypt structures, suggesting that this pathway may contribute to the acquisition of stem-like properties.
The dedifferentiation-derived cells showed growth-factor independence, which allows them to proliferate without relying on the supportive niche environment normally required by stem cells. They also exhibited metabolic adaptations associated with tumor survival.
The study also found evidence of stem-cell heterogeneity within tumors. Single-cell analysis identified populations with distinct proliferative, signaling, and metabolic states. One mutant stem-cell cluster exhibited cancer-associated and embryonic stem cell-like gene signatures, while other clusters appeared more quiescent.
“Our findings suggest that metabolic adaptations and dedifferentiation-driven stem cell heterogeneity may enhance adaptability and confer a selective advantage driving top-down tumorigenesis,” the researchers wrote.
The findings have implications for current and future treatment strategies. Many therapies focus on eliminating actively growing cancer cells, but the study suggests that stem-like cells generated through dedifferentiation may remain capable of regenerating tumors after treatment. Targeting the mechanisms that enable mature epithelial cells to revert to a stem-like state could prove an effective method for preventing cancer recurrence.
“If you are only treating the cells that become cancerous without targeting the cells that acquired the de novo stemness, the cancer will likely come back,” Perekatt said. “So it’s really important to understand what causes this reversion to stemness, in order to develop new and effective therapies for colorectal cancers.”
Future research will focus on unanswered questions raised by the study, including the source of the Notch signals that trigger dedifferentiation, the transcriptional programs activated during this process, and the metabolic vulnerabilities of the resulting stem-like tumor cells.
The post Mature Intestinal Cells Revert to Stem-Like State to Sustain Colorectal Cancer appeared first on Inside Precision Medicine.