Preclinical and randomized clinical evaluation of the p38α kinase inhibitor neflamapimod for basal forebrain cholinergic degeneration

Preclinical study design

Mouse experimentation and animal care were approved by the Institutional Animal Care and Use Committee (IACUC) of the Nathan S. Kline Institute. Ts2 (Stock No. 004850) mice, and wild type breeding partner (B6EiC3SnF1/J, Stock No. 001875) from the same colony were obtained from The Jackson Laboratory (Bar Harbor, ME). The protocol for drug dosage and oral gavage procedure was approved by the IACUC committee of Nathan S. Kline Institute (NKI) and renewed every three years, with the current protocol number AP2021-685-NKI.

The test compound neflamapimod (manufacturer lot number M10140) and instructions for formulation preparation, route of administration and dosing volume were provided by EIP Pharma, Inc. Both wild-type (2 N) and Ts2 mice were treated for four weeks, twice-daily by oral gavage at a 5 ml/kg dosing volume with vehicle (1% (w/v) Pluronic F108,…

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