Authier, Simon, Delatte, Marcus S, Halpern, Wendy, Mellon, Dan, B Rao, Deepa, Traebert, Martin, Valentin, Jean-Pierre, Sokolowski, Katie and Pugsley, Michael K (2025) Neurotoxicology and Safety Pharmacology Investigations on the Nervous System: 2024 Industry Survey. Journal of Pharmacological and Toxicological Methods.

Abstract

The American College of Toxicology (ACT), the Safety Pharmacology Society (SPS) and the Society for Toxicological Pathology (STP) conducted an industry survey in 2024 to assess industry practices as they relate to neurotoxicity and safety testing of neurotherapeutics. One hundred thirty (130) respondents from Asia (5%), Europe (32%) and North America (64%) responded to the survey. Most respondents (54%) were from pharmaceutical companies (>1000 employees). Small molecules (89%), large molecules (73%), gene therapy (52%), cell therapy (41%) and vaccines (38%) were the types of products developed by respondents. Oncology (72%) and neurology/psychiatry (64%) were the most frequent target indications pursued by companies followed by inflammation (56%), cardiovascular (48%), rare/orphan (44%), metabolic (42%), infectious (35%) and respiratory (28%) diseases. Tremors (81%), emesis (75%), gait/coordination abnormalities (67%), convulsion (65%), salivation (61%) and peripheral neuropathy (24%) were the most encountered CNS issues in pre-clinical drug development while headache (59%), emesis/nausea (49%), dizziness (45%), fatigue (30%) and tremors (19%) were the most frequent issues encountered in Phase I clinical trials. Most respondents reported using a modified Irwin’s test (90%) added to toxicology studies (80%) or using a standalone study (71%). Implanted EEG was the most frequently used electrophysiology methodology (66%) while stem cell derived neurons were the most frequent in vitro methodology (50%). The rat was reported as the most common species used for functional observation battery (FOB) (91%), EEG (70%), seizure liability (84%) and juvenile CNS studies (84%).

Item Type:	Article
Keywords:	neurotoxicity, safety pharmacology CNS, FOB, Irwin test, seizures, convulsions, EEG
Date Deposited:	05 Aug 2025 00:45
Last Modified:	05 Aug 2025 00:45
URI:	https://oak.novartis.com/id/eprint/56134