Tag: Medication

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STAT+: Pharmalittle: We’re reading about a U.S. peptide panel’s votes, Amgen scuffling with the FDA, and more

Good morning, everyone, and welcome to another working week. We hope the weekend respite was relaxing and invigorating because that oh-too-familiar routine of meetings, deadlines, and the like has returned with a vengeance. You knew this would happen, yes? To cope, we are relying, as always, on a cuppa stimulation. Our choice today is Earl Grey, an old standby. Feel free to join us. Remember, no prescription is required. Meanwhile, here are some items of interest to help you on your journey today, which we hope will be productive and meaningful. Best of luck and, of course, do keep in touch. …

A U.S. Food and Drug Administration advisory panel on Friday recommended that compounding pharmacies be allowed to manufacture the peptides epitalon and semax, but narrowly voted to recommend against manufacturing emideltide, STAT writes. The votes, which followed the panel’s decision on Thursday to recommend allowing pharmacies to make four other peptides, bring U.S. Health and Human Services secretary Robert F. Kennedy Jr. one step closer to his mission of making these unapproved compounds more available for Americans. Peptides have become increasingly popular in the U.S., driven by endorsements from social media influencers.

Amgen submitted new evidence to the FDA ​as it seeks a hearing to challenge the proposed ‌withdrawal of its rare disease drug Tavneos from the U.S. market, Reuters says. In April, the agency proposed withdrawing the drug, which treats a rare autoimmune ​disease that damages blood vessels, citing a lack of proven effectiveness ​and false statements in its original marketing application. Amgen strongly disagrees with the FDA and noted its submission includes more than 70 real-world studies involving over ​2,200 patients supporting the drug’s effectiveness and safety.

Continue to STAT+ to read the full story…

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Resting-state functional connectivity of the sensorimotor network in medication-naïve Chinese children with ADHD: cross-sectional associations with hyperactivity/impulsivity and executive function

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder, often—but not always—characterized by inattention, hyperactivity/impulsivity, and deficits in executive functions (EFs); some individuals may also exhibit sensorimotor dysfunction. While SMN dysfunction has been implicated in ADHD, the patterns of SMN functional connectivity (FC) and their relationships with clinical symptoms and EFs remain inconsistent, partly due to methodological heterogeneity.MethodsThe study included 62 medication-naïve patients with ADHD (aged 6–15 years) and 46 healthy controls matched for age, sex, and IQ. Clinical symptoms and EFs were assessed using CPRS, IVA-CPT, and Stroop tests. Resting-state fMRI data were acquired, and ROIs within SMN, SN, DMN, and FPN were selected from the Dosenbach atlas. FC was analyzed using Network-Based Statistics (NBS). Partial correlations explored FC–behavior relationships in the ADHD group, controlling for age, sex, and IQ.ResultsThe ADHD group showed significantly higher CPRS hyperactivity/impulsivity scores and poorer IVA-CPT and Stroop performance. Compared to controls, ADHD showed increased FC within SMN (right posterior insula to left precentral gyrus/parietal lobe), between SMN–DMN (precentral gyrus, dorsal frontal cortex, temporal lobe, angular gyrus, posterior cingulate cortex, and precuneus), and SMN–SN (middle insula, superior parietal lobule, superior temporal gyrus, basal ganglia, and fusiform gyrus). Enhanced intra-SMN FC was negatively correlated with impulsivity/hyperactivity and hyperactivity index scores. Enhanced SMN–DMN FC was negatively correlated with hyperactivity symptoms and positively correlated with control quotients in IVA-CPT. Enhanced SMN–SN FC was negatively correlated with Stroop correct responses and positively correlated with omission errors.ConclusionsIn this medication-naïve pediatric sample, distinct SMN connectivity patterns differentially related to ADHD symptoms and executive function. However, given the cross-sectional design and modest sample size, these associations cannot establish causality; they require replication in longitudinal studies and larger cohorts to clarify whether they reflect developmental variation, neurobiological subtypes, or epiphenomena.
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Autonomic dysregulation and nonsuicidal self-injury: findings from a cross-sectional online survey

IntroductionDysregulation of the autonomic nervous system has been implicated in nonsuicidal self-injury (NSSI) in laboratory studies of physiological reactivity, but it remains unclear whether self-reported everyday autonomic symptom burden is associated with NSSI severity.MethodsWe conducted a preregistered cross-sectional online survey of N = 1,002 German-speaking adolescents and young adults aged 14–30 years (M = 23.43; 73% women). Autonomic symptoms were assessed with the COMPASS 31; NSSI presence and frequency were measured with the SITBI-R across four reference periods (past week, month, year, lifetime). Data were analyzed using zero-inflated negative binomial models.ResultsThe 12-month NSSI prevalence was 22.6%. Higher COMPASS 31 scores were associated with lower odds of reporting zero NSSI episodes across all reference periods and with higher NSSI episode counts for the past month, past year, and lifetime; the past-week count association was not statistically significant. These associations held after controlling for childhood adversity, perceived stress, medication, and hormonal contraception.DiscussionThese results indicate that self-reported autonomic symptom burden was robustly associated with NSSI involvement, particularly with the likelihood of any NSSI and with episode counts over longer reference periods. These findings suggest that self-reported autonomic symptom burden may represent a clinically relevant somatic correlate of NSSI severity.
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STAT+: RA Capital backs upstart rival to Ultragenyx and Ionis in rare brain disease

RA Capital and a fleet of other investors are putting $175 million behind Oak Hill Bio, a startup trying to revive an experimental Angelman syndrome drug that Roche shelved. 

Oak Hill is competing with Ultragenyx Pharmaceutical and Ionis Pharmaceuticals, both of which are already running Phase 3 trials of similar drugs for the same disease. Ultragenyx will have results this year.

Oak Hill is betting it has the best molecule.

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STAT+: As some medical schools embrace RFK Jr.’s nutrition push, they deftly sidestep MAHA priorities

When students return to McGovern Medical School at UT Health Houston this year, they will get to participate in hands-on nutrition experiences, including cooking demonstrations in the teaching kitchen, tours of the campus “holistic garden,” and the opportunity to take a culinary-medicine-focused elective. 

These immersive programs are a response to health secretary Robert F. Kennedy’s call for medical schools to teach more nutrition — part of the Trump administration’s push to address the rising rates of chronic diseases in the United States. Kennedy has blamed the problem, in part, on doctors not routinely discussing diet and nutrition with their patients.

Lessons in culinary medicine are part of the 71 nutrition-related topics that the Department of Health and Human Services wants future physicians to be well versed in. Other topics in the department’s Advancing Nutrition Education push include enhancing nutrient bioavailability through soaking, sprouting, and fermenting foods as well as prioritizing food-based medicine as the primary approach to manage chronic diseases driven by metabolic dysfunction.

The vast majority of 163 M.D.-granting and 48 D.O.-granting schools aren’t yet part of Kennedy’s new initiative, including several leading institutions. So far, some 73 medical schools — 54 M.D. programs, 19 D.O. programs — across 36 states have signed on.

Even as some medical schools heed Kennedy’s call for more nutrition education, several told STAT that they plan to steer clear of topics that aren’t backed by evidence, including some that align with the priorities of the Make America Healthy Again political movement championed by the health secretary. Nutrition experts cautioned that some of those topics could lead to “wellness creep” in medical education.

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Molecular Atlas of Severe Preeclampsia Reveals New Therapeutic Targets

Researchers from University College London in England have created the most comprehensive molecular map to date of severe preeclampsia, uncovering distinct fetal and maternal drivers of the disease that could lead to more targeted therapies and earlier intervention.

The study, published in Science Advances, combined single-cell RNA sequencing with spatial transcriptomics across the entire fetal-maternal interface and found that severe preeclampsia is not solely a placental disorder. Instead, the disease involves coordinated dysfunction across multiple maternal and fetal tissues, with different molecular programs emerging in early- versus late-onset disease.

Preeclampsia affects 2% to 4% of pregnancies worldwide and remains a leading cause of maternal and fetal illness and death. Although it is traditionally viewed as a placental disease, the mechanisms responsible for widespread maternal inflammation and endothelial dysfunction have remained unclear.

To better define those mechanisms, investigators analyzed tissues from 20 pregnancies, including 10 women with severe preeclampsia and 10 gestational age-matched controls between 25 and 37 weeks of gestation. By matching pregnancies by gestational age rather than comparing preterm cases with healthy term pregnancies, the researchers were able to distinguish disease-related molecular changes from normal developmental differences.

The analysis revealed extensive placental abnormalities, including molecular signatures of hypoxia, angiogenic imbalance, fibrosis, and altered metabolism. The team also confirmed impaired invasion of fetal extravillous trophoblasts into the maternal uterus, a hallmark of preeclampsia that contributes to defective remodeling of maternal blood vessels.

Beyond the placenta, however, the study identified previously unrecognized maternal immune abnormalities extending into the myometrium and chorioamniotic membranes. These included widespread mitochondrial dysfunction, activation of type I interferon signaling, and altered macrophage responses, providing a potential explanation for the systemic inflammation and endothelial injury that characterize severe disease.

The findings point to several potential therapeutic targets. Leptin (LEP), which was strongly upregulated in placental cells throughout both early and late disease, may contribute to oxidative stress and vascular dysfunction. The researchers suggest that leptin antagonists, already under investigation for autoimmune diseases, warrant exploration as placental-targeted therapies.

The study also highlights type I interferon signaling as a promising target. Elevated interferon activity, detected in maternal immune cells and peripheral blood, could potentially serve as both a biomarker and a therapeutic target for anti-interferon or antioxidant treatments.

“IFN-I in peripheral blood promises better screening of patients that might benefit from anti-IFN or antioxidant therapeutics,” the authors concluded.

Perhaps most importantly, the molecular abnormalities were substantially more pronounced in early-onset disease, suggesting that intervention before clinical deterioration may offer the greatest benefit.

“Given the severity of molecular dysfunctions in early disease, compared to its late presentation, timely intervention during gestation is likely beneficial and could change the extremely poor prognosis of severe PE,” the authors wrote.

The post Molecular Atlas of Severe Preeclampsia Reveals New Therapeutic Targets appeared first on Inside Precision Medicine.

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Genetic Variants Linked to CAR T-Cell Efficacy and Safety

Scientists have identified variants in three genes that influence both the efficacy of CAR T-cell therapy and the likelihood of severe side effects. Published today in Science Immunology, these findings represent a first step toward adopting a precision medicine approach in an increasingly used form of cancer immunotherapy. 

CAR T-cell therapies have undeniably transformed the treatment of blood cancers, with a rapidly growing number of approvals over the past decade and progressively expanding toward solid tumors. While genetic variants associated with immune-related side effects have been identified for other forms of cancer immunotherapy, such as checkpoint inhibitors, the role of human genetics in CAR T-cell therapy has remained largely unexplored. However, this is particularly important given that most CAR T cells are manufactured from a patient’s own immune cells, meaning the therapy itself carries the patient’s unique genetic makeup. 

“Unlike traditional therapeutics that are essentially identical across all patients, CAR T cells are bespoke and harbor all of the ancestral genetic polymorphisms of their parental T cells,” write the study authors, led by Marcela V. Maus, MD, PhD, professor of medicine at Harvard Medical School and director of the Cellular Immunotherapy Program at Massachusetts General Hospital. 

Maus and colleagues analyzed data from 236 patients with aggressive lymphoma enrolled across two clinical trials, who had been treated with axicabtagene ciloleucel, a CAR T-cell therapy commercialized by Gilead under the name Yescarta. The analysis combined whole-genome sequencing with detailed biomarker and functional analysis to identify variants affecting the treatment’s efficacy and toxicity.

Among patients who developed treatment-induced toxicity, many carried variants of the STXBP2 gene. Follow-up experiments in human T cells showed that these variants increased the production of inflammatory cytokines and activated macrophages. Consistent with these findings, mutations in the STXBP2 gene have previously been linked to inflammatory bowel disease and a rare immune disease marked by excessive T cell activation. 

In contrast, variants in the ADMTSL3 gene were associated with protection against treatment-related toxicity, while variants in the PTPN22 gene were strongly linked to enhanced CAR T-cell expansion—a critical factor that determines treatment efficacy.  

“These findings demonstrate that germline genetics shape the safety and activity of engineered immune cell therapies, affecting future design and patient management,” write the scientists. Going forward, they plan to expand this research into larger patient cohorts and a wider range of CAR T-cell therapies to investigate how different genetic variants influence treatment efficacy and the risk of severe side effects across broader clinical settings. 

Beyond opening new avenues for precision medicine in CAR T-cell therapy, the researchers noted that these findings could also inform the development of off-the-shelf CAR T-cell therapies where donor-derived T cells are used instead of a patient’s own cells. This approach could enable a more precise selection of donor T cells optimized to maximize therapeutic benefit while minimizing toxicity risks. 

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Gut Bacteria Chemical Linked to Irregular Heart Beat

A chemical called trimethylamine N-oxide (TMAO), which originates from gut bacteria digesting animal products such as red meat, is present at higher levels in the blood of people with an irregular heart beat than the rest of the population.

The researchers found that after they had controlled for various factors like age and comorbidities, people in the top third of TMAO levels had a 70% increased risk of having atrial fibrillation compared with those in the bottom third.

Atrial fibrillation is the most common sustained heart rhythm disorder in the U.S. impacting more than 10 million adults. It occurs because the upper chambers of the heart beat rapidly and irregularly, which can lead to blood clots, stroke and heart failure if left unchecked.

TMAO is formed when trimethylamine produced by gut bacteria is carried to the liver and oxidized. Animal-derived foods such as red and processed meat, eggs, high fat dairy products, and some supplements, are the main dietary precursors for production of TMAO. It has previously been linked to increased risk of cardiovascular disease more generally, but whether high levels of this chemical increased risk of atrial fibrillation was less clear.

In this study, published in the journal of Journal of Clinical Investigation, lead investigator Robert Koeth, MD, PhD, a clinician scientist based at the Cleveland Clinic, and colleagues assessed blood TMAO levels in 5,000 adults who underwent elective heart catheterization for known or suspected cardiovascular disease.

They also studied the effects of TMAO on heart beat regularity in model mice susceptible to atrial fibrillation and tested a potential candidate drug to see if it could reduce levels of TMAO in these animals.

After controlling for age, sex, diabetes, cardiovascular disease, blood pressure, smoking, body mass index, inflammation and kidney function, people with the highest TMAO levels had about 1.7‑times the odds of having atrial fibrillation compared with people with the lowest levels.

In the mouse studies, when TMAO levels in the blood were higher, the animals developed atrial fibrillation sooner and it became a persistent problem more quickly. The researchers also saw changes in how electrical signals moved through parts of the heart that made it easier for abnormal rhythms to start and continue.

The researchers tested iodomethylcholine in the mice, an experimental small molecule drug that blocks the gut microbial enzyme responsible for converting choline into trimethylamine. In response to the drug, TMAO levels fell, the mix of gut bacteria changed, and both the first episodes of atrial fibrillation and its progression were delayed without notable negative effects on the liver.

“A possible pathogenic culprit for the development of atrial myopathy and electromechanical dysfunction is chronic autonomic dysfunction from TMAO inhibition of the M2 muscarinic acetylcholine receptor and increasing sympathetic tone,” write Koeth and team.

The results suggest “TMAO promotes atrial fibrillation in a gut microbiota dependent manner by causing autonomic dysfunction, atrial myopathy, and electromechanical dysfunction,” they conclude.

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