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Neurotoxicity

Approximately one quarter of small molecules in drug development intended for CNS indications fail in clinical trials due to neurotoxicity issues, which are often not identified during early drug discovery stages. This leads to wasted resources and unknowingly exposing patients to potential side effects. To address this, Ekam has developed an imaging protocol called “in vivo neuropathology” which uses DWI and ADC measures along with a 3D MRI rat atlas to identify sites of neuroinflammation and edema after exposure to neurotoxins. This non-invasive approach allows for time-dependent neuropathology studies, guiding histopathology in preclinical drug development, while minimizing the number of animals used in testing. “In vivo neuropathology” can help minimize costs and expedite preclinical CNS toxicology, while detecting subtle changes in brain microarchitecture.

Reference:

Ferris CF, Kulkarni P. In vivo Neuropathology: Detecting the Neurotoxicity of Candidate Drugs during Early Drug Discovery. J Exp Neurol. 2021;2(4):177-178.

Praveen Kulkarni, Nicole Bens, Dhruv K. Karia, Craig F. Ferris,.Whole brain in vivo neuropathology: Imaging site-specific changes in brain structure over time following trimethyltin exposure in rats,Toxicology Letters,Volume 352, 2021, Pages 54-60, ISSN 0378-4274, https://doi.org/10.1016/j.toxlet.2021.09.009.