The Feinstein Institutes for Medical Research

MANHASSET, N.Y.--(BUSINESS WIRE)--Researchers at Northwell Health’s Feinstein Institutes for Medical Research have developed an artificial intelligence (AI)-based tool that identifies a brain metabolic network capable of predicting psychosis in Alzheimer's disease (AD). This discovery, published this week in Brain Communications, offers a potential breakthrough for earlier diagnosis, treatment development and personalized medicine for individuals with AD. The study, led by Jeremy L. Koppel, MD, associate professor at the Feinstein Institutes’ Institute of Molecular Medicine, and associate professor An Vo, PhD, used an AI-derived metabolic brain map that looks at FDG-PET scans of people with AD, including some who experienced psychosis (hallucinations and delusions) and some who did not. The AI identified a unique pattern of brain activity, like a fingerprint, in the brains of those with psychosis. They called this pattern the ADPN (Alzheimer's Disease Psychosis Network). “This discovery of the ADPN provides a critical tool for advancing our understanding and management of psychosis in Alzheimer’s disease,” said Dr. Koppel. “This biomarker can potentially identify individuals at risk of developing psychosis, allowing for earlier and more targeted interventions.” Psychosis, characterized by delusions and hallucinations, affects a significant portion of individuals with AD and is associated with accelerated cognitive decline, increased caregiver burden and premature mortality. Current treatments are limited and often carry significant risks. The ADPN, however, was helpful in distinguishing the difference in brain patterns between people with AD and psychosis, especially between the areas responsible for movement and the areas responsible for language and social understanding. It was also able to predict who would develop psychosis in the future. The stronger the ADPN “fingerprint,” the worse the person’s cognitive decline. “The discovery of the ADPN exemplifies the power of AI and interdisciplinary collaboration in advancing our understanding of complex neurological disorders like Alzheimer’s disease,” said Kevin J. Tracey MD, president and CEO of the Feinstein Institutes and Karches Family Distinguished Chair in Medical Research. “This innovative approach, integrating neuroimaging with cutting-edge computational tools, offers a new path towards earlier diagnosis, personalized treatment strategies, and ultimately, improved outcomes for individuals affected by this devastating disease.” Dr. Koppel is an internationally recognized clinical scientist who continues to identify AD’s potential causes and treatments. He recently received a National Institutes of Health grant for nearly $500,000 to look at ptau181 and other biomarkers in psychosis before AD begins as well as a $1 million grant from the Alzheimer's Foundation of America to expand research into developing new treatments to address the hallucinations, delusions and aggression that come with dementia. Last year, he and his lab published in the Journal of the American Medical Association (JAMA) Psychiatry papers that showed an increase in specific tau proteins that indicated blood biomarkers could be used to detect psychotic symptoms in AD patients. About the Feinstein Institutes The Feinstein Institutes for Medical Research is the home of the research institutes of Northwell Health, the largest health care provider and private employer in New York State. Encompassing 50+ research labs, 3,000 clinical research studies and 5,000 researchers and staff, the Feinstein Institutes raises the standard of medical innovation through its six institutes of behavioral science, bioelectronic medicine, cancer, health system science, molecular medicine, and translational research. We are the global scientific leader in bioelectronic medicine – an innovative field of science that has the potential to revolutionize medicine. The Feinstein Institutes publishes two open-access, international peer-reviewed journals Molecular Medicine and Bioelectronic Medicine. Through the Elmezzi Graduate School of Molecular Medicine, we offer an accelerated PhD program. For more information about how we produce knowledge to cure disease, visit http://feinstein.northwell.edu and follow us on LinkedIn.

MANHASSET, N.Y.--(BUSINESS WIRE)--Inflammation is the body’s response to injury and infection. To better understand how the body’s nerves and neurons detect inflammation, researchers at Northwell Health’s Feinstein Institutes for Medical Research have shown how vagus nerve immune signals are encoded and communicated to the brain and how inflammation caused by conditions like colitis can disrupt this neuro-immune signaling. The study, led by Eric H. Chang, PhD, associate professor in the Institute of Bioelectronic Medicine at the Feinstein Institutes, and published this week in Nature Communications, focuses on sensory neurons of the vagus nerve, a major communication pathway between the body and the brain. The researchers used advanced calcium imaging techniques to observe the activity of individual sensory neurons within the nodose ganglion, a cluster of nerve cells that forms part of the vagus nerve. They found that different inflammatory signals, called cytokines, activate distinct patterns of neural activity in individual neurons. Some neurons respond selectively to only one cytokine, while others respond to multiple cytokines but maintain the unique cytokine-specific activity signatures. While it was previously known that cytokines are released in the body during inflammation, how the nervous system detects and represents these immune signals was unclear. “This research unveils a previously unrecognized complexity in how sensory neurons in the peripheral nervous system of the body communicate immune signals to the brain,” said Dr. Chang. “It provides insights about the precise neural mechanisms used to encode immune information, offering potential new avenues to diagnose and treat disorders of the neuro-immune axis.” The researchers also discovered that inflammation caused by colitis alters the activity of these sensory neurons. Inflammation increases the baseline activity of these neurons but reduces their ability to respond precisely to specific cytokines. In other words, inflammation “scrambles” the neuro-immune nerve signals, potentially disrupting how the brain regulates the immune response and contributing to conditions such as autoimmune disease and chronic inflammatory disorders. “The brain controls the amount of inflammation in the body, and nerves in the body inform the brain about the extent of inflammation,” said Kevin J. Tracey, MD, president and CEO of the Feinstein Institutes and Karches Family Distinguished Chair in Medical Research. “The discoveries in this important paper reveal how the vagus nerve transmits specific electrical signals to the brain about inflammation in a gut-vagus-brain axis.” The Feinstein Institutes for Medical Research is the global scientific home of bioelectronic medicine, which combines molecular medicine, neuroscience and biomedical engineering. At the Feinstein Institutes, medical researchers use modern technology to develop new device-based therapies to treat disease and injury. Building on years of research in molecular disease mechanisms and the link between the nervous and immune systems, Feinstein Institutes’ researchers discovered neural targets that can be activated or inhibited with neuromodulation devices, like vagus nerve implants, to control the body's immune response and inflammation. If inflammation is successfully controlled, diseases – such as arthritis, pulmonary hypertension, heart failure, inflammatory bowel diseases, diabetes, cancer and autoimmune diseases – can be treated more effectively. Beyond inflammation, using novel brain-computer interfaces, Feinstein Institutes' researchers developed techniques to bypass injuries of the nervous system so that people living with paralysis can regain sensation and use their limbs. By producing bioelectronic medicine knowledge, disease and injury could one day be treated with our own nerves without costly and potentially harmful pharmaceuticals. About the Feinstein Institutes The Feinstein Institutes for Medical Research is the home of the research institutes of Northwell Health, the largest health care provider and private employer in New York State. Encompassing 50+ research labs, 3,000 clinical research studies and 5,000 researchers and staff, the Feinstein Institutes raises the standard of medical innovation through its six institutes of behavioral science, bioelectronic medicine, cancer, health system science, molecular medicine, and translational research. We are the global scientific leader in bioelectronic medicine – an innovative field of science that has the potential to revolutionize medicine. The Feinstein Institutes publishes two open-access, international peer-reviewed journals Molecular Medicine and Bioelectronic Medicine. Through the Elmezzi Graduate School of Molecular Medicine, we offer an accelerated PhD program. For more information about how we produce knowledge to cure disease, visit http://feinstein.northwell.edu and follow us on LinkedIn.

Treatment with LB-102 resulted in a positive shift in disease severity as measured by mean change from baseline in Clinical Global Impression of Severity (CGI-S) scores Phase 3 clinical trial of LB-102 in acute schizophrenia expected to initiate in Q4 2025 NEW YORK, March 31, 2025 (GLOBE NEWSWIRE) -- LB Pharmaceuticals Inc., a clinical-stage biopharmaceutical company developing novel therapies for the treatment of neuropsychiatric diseases including schizophrenia, today presented additional positive data from NOVA1, a Phase 2 clinical trial of LB-102 in acutely exacerbated schizophrenia patients, at the 2025 Annual Congress of the Schizophrenia International Research Society (SIRS) being held in Chicago, Illinois, from March 29 to April 2, 2025. As previously reported the primary endpoint of NOVA1, a clinically meaningful change in Positive and Negative Syndrome Scale (PANSS) total score at week 4, was achieved with a high degree of statistical significance at all doses. The study also measured mean change from baseline in Clinical Global Impression of Severity (CGI-S) score, which rates illness severity on a scale from 1 (normal) to 7 (extremely ill) and has been shown to correlate with PANSS, as a secondary endpoint. At week 4 of the study, participants treated with the 50 mg dose (n=107) achieved a mean change in baseline CGI-S score of -0.72 compared to placebo (p=0.0008). Those who received the 75 mg dose (n=108) achieved a mean change in baseline CGI-S score of -0.67 compared to placebo (p=0.0048). Treatment with the exploratory dose of 100 mg (n=36) resulted in a mean change in baseline CGI-S score of -0.84 compared to placebo (p=0.0026). "The significant improvement in CGI-S scores observed in NOVA1 reinforces that LB-102 may provide a meaningful clinical impact on disease severity and further validates its strong potential as a next-generation treatment for schizophrenia,” said Heather Turner, Chief Executive Officer of LB Pharmaceuticals. “These results support our vision for LB-102 as a therapy that provides a compelling balance of efficacy and safety, addressing the urgent need for better-tolerated, efficacious therapies for people with schizophrenia. As we advance toward the initiation of a Phase 3 clinical trial in Q4 2025, this data strengthens our confidence in LB-102 as a first-in-class benzamide antipsychotic in the United States.” Treatment with LB-102 was generally safe and well-tolerated. The most common adverse events were insomnia, headache, anxiety, and agitation, consistent with existing antipsychotics. Increases in prolactin were observed with few clinical adverse events associated with those increases. Modest weight gain was also observed but was not associated with a clinically meaningful signal in metabolic parameters. John M. Kane, M.D., Professor of Psychiatry and Molecular Medicine at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, the Co-Director of the Institute for Behavioral Science at the Feinstein Institutes for Medical Research, and the Principal Investigator of NOVA1, added, “These CGI-S scores are compelling. In combination with the statistically significant change from baseline in the PANSS total scores, the findings of NOVA1 reflect the potential real-world clinical impact of LB-102 on patients with acute schizophrenia. While PANSS scores provide a structured measure of symptom changes, CGI-S offers an independent, clinician-driven, assessment of overall disease severity. The meaningful reductions in CGI-S scores suggest that study participants are experiencing not just statistical improvement, but tangible, clinically relevant benefits that could translate to better daily quality of life. Given the ongoing need for effective and well-tolerated treatment options, these findings further support the potential of LB-102 to help address a critical gap in schizophrenia care.” About NOVA1The Phase 2 randomized, double-blind, placebo-controlled, multi-center inpatient trial enrolled 359 adults, age 18 to 55 with DSM-5 diagnosis of acutely exacerbated schizophrenia. The trial evaluated the efficacy and safety of a once-daily oral dose of LB-102. The primary objective of the study assessed the efficacy of LB-102 versus placebo in reducing Positive and Negative Syndrome Scale (PANSS) total scores at day 28. The secondary objectives of the study included improvement in CGI-S, PANSS subscale and Marder Factor scores, safety and tolerability, and pharmacokinetics. Randomization was approximately 3:3:3:1 as participants received either placebo, 50 mg QD LB-102, 75 mg QD LB-102, or 100 mg QD LB-102. About LB-102LB-102 is a potent antagonist of dopamine D2/3 and 5HT7 receptors with low off-target activity. In a Phase 2 clinical study of once-daily orally administered, LB-102 meaningfully improved symptoms of schizophrenia. A Phase 3 clinical study is planned to begin later in 2025. Based on the mechanism of action and preclinical studies, clinical trials of LB-102 are being planned in bipolar depression, predominantly negative schizophrenia, and Alzheimer’s agitation/psychosis, in addition to other psychiatric indications. The first of these studies is expected to begin in 2026. If approved, LB-102 would be the first benzamide in the U.S. to treat psychiatric disorders. About LB PharmaceuticalsLB Pharmaceuticals is a clinical-stage biopharmaceutical company developing novel therapies for the treatment of neuropsychiatric diseases, including schizophrenia. The company’s lead candidate, LB-102, is a potential first-in-class benzamide antipsychotic in the U.S. designed to address critical gaps in the current standard of care by providing comprehensive disease management with a generally safe and tolerable profile. LB Pharmaceuticals is backed by institutional investors Deep Track Capital, TCGx Crossover, Vida Ventures, and Pontifax. To learn more, visit our website at https://lbpharma.us/. Media Contact: Michael Fitzhugh LifeSci Communications mfitzhugh@lifescicomms.com