Liss' Lowdown #22

Preclinical Breakthrough of the month:

Unveiling Substance Influence on Brain Cell Connections: A Preclinical Meta-Analysis

耶鲁大学 researchers have discovered that investigating the impact of substances on the density of connections between brain cells provides valuable insights into the mechanisms underlying substance use. Animal studies demonstrate that alcohol, amphetamine, cannabis, cocaine, opioids, and nicotine alter synaptic density markers like spine density, potentially influencing behaviours such as sensitization and drug self-administration. However, findings across substances and brain regions vary. A meta-analysis of 70 preclinical studies reveals drug-specific patterns: amphetamine increases hippocampal spine density, while amphetamine, cocaine, and nicotine boost density in the nucleus accumbens. Alcohol and amphetamine increase, and cannabis decreases, prefrontal cortex spine density. Morphine effects are inconsistent. Cocaine's prefrontal cortex effects contradict human studies, warranting further investigation. Notable publication bias exists for cocaine and nicotine. Despite heterogeneity, these findings advance translational efforts in understanding substance use disorder mechanisms in humans.

Clinical Breakthrough of the month:

KarXT Shows Long-Term Efficacy in Reducing Schizophrenia Symptoms

百时美施贵宝 unveils interim findings from the Phase III EMERGENT-4 trial, showcasing KarXT's efficacy in reducing schizophrenia symptoms in adults. The 52-week outpatient study assessed the long-term safety and effectiveness of the muscarinic antipsychotic in patients who had completed Phase III EMERGENT-2 or EMERGENT-3 trials.

Results from 110 patients, including 29 who completed a year of treatment, demonstrated significant symptom improvement measured by PANSS scores, with over 75% experiencing >30% reduction. Notably, KarXT recipients showed a mean 1.7-point shift in CGI-S score from 'markedly ill' to 'moderately' or 'mildly' ill. Benefits persisted regardless of initial placebo or KarXT treatment. Those transitioning from placebo experienced rapid symptom improvement within two weeks, reaching comparable PANSS scores to KarXT recipients by four weeks. Moreover, KarXT exhibited positive effects on weight and metabolic parameters, maintaining a favorable side effect profile consistent with prior trials. BMS is encouraged by these sustained results and anticipates further discussions with the FDA, aiming to share additional EMERGENT program data later this year.

Partnership of the month:

Scantox Completes Acquisition of QPS Neuropharmacology, Expands CNS Research Capabilities

Last week Scantox Group , in collaboration with majority owner Impilo , completed the acquisition of QPS Neuropharmacology , now operating as Scantox Neuro GmbH . Renowned for its high-quality services in neurodegenerative diseases, rare conditions, and mental disorders, QPS Neuropharmacology brings extensive expertise and a strong global customer base to the Scantox Group. With this acquisition, Scantox significantly enhances its value chain, particularly in central nervous system (CNS) research. QPS Neuropharmacology, founded in 1999, boasts a state-of-the-art facility in Austria and over 80 employees. Its specialization in lead optimization services and efficacy studies, coupled with validated in-vitro and in-vivo models, positions it as a vital partner for biotech and pharma companies in drug development. The integration expands Scantox's Discovery division, enriching its service offerings in the CNS and rare disease domain.

Scantox Group now comprises over 300 employees across six sites, offering lead optimization, regulatory toxicology, and CMC/analytical services. This acquisition marks a significant step for Scantox in broadening its service spectrum and customer base, as emphasized by Jeanet L?gsted , CEO of Scantox Group, and Manuela Prokesch , Head of Scantox Neuro GmbH. Impilo's Partner Nicholas Hooge highlights the growth potential of the combined business.