Novaremed: Data of drug candidate for the prevention of chemotherapy-induced peripheral neuropathy

“We are delighted with the publication of these data on MP-101,” said Eva Tiecke, PhD, Chief Scientific Officer and Head of R&D of Novaremed. “The study demonstrated that MP-101, a non-racemic enantiomeric mixture containing three parts of R-dimiracetam and one part of S-dimiracetam, is pharmacologically more potent than racemic dimiracetam in several animal models of neuropathic pain, cognition, and depression. The demonstrated efficacy of MP-101 in the oxaliplatin-induced peripheral neuropathic pain model, together with the preclinically and clinically established safety and tolerability profile of racemic dimiracetam, strongly support the development of MP-101 for the prevention of symptoms of peripheral neuropathy, including neuropathic pain induced by chemotherapy, an area with a high unmet medical need.”

In this study [1], the effects of dimiracetam, its R- or S-enantiomers, and the R:S 3:1 nonracemic mixture, designated as MP-101, were compared. In vitro, dimiracetam was more potent than its R- or S-enantiomers in reducing the N-methyl-D-aspartate (NMDA)-induced [3H]D-aspartate release in rat spinal cord synaptosomes. Similarly, acute oral administration of dimiracetam was more effective than a single enantiomer in the sodium monoiodoacetate (MIA) paradigm of painful osteoarthritis. Then, the in vitro effects of a broad range of non-racemic enantiomeric mixtures on the NMDA-induced [3H]D-aspartate release were compared. Dimiracetam was a more potent blocker than each isolated enantiomer but the R:S 3:1 non-racemic mixture (MP-101) was even more potent than dimiracetam, with an IC50 in the picomolar range. In the chronic oxaliplatin-induced neuropathic pain model, MP-101 showed a significantly improved anti-neuropathic profile, and its effect continued one week after treatment suspension. MP-101 also performed better than dimiracetam in animal models of cognition and depression. Based on the benign safety and tolerability profile previously observed with racemic dimiracetam, MP-101 appears to be a novel, promising clinical candidate for the prevention and treatment of several neuropathic and neurological disorders.

Reference:
[1] Bonifacino, T.; Micheli, L.; Torazza, C.; Ghelardini, C.; Farina, C.; Bonanno, G.; Milanese, M.; Di Cesare Mannelli, L.; Scherz, M.W. Pharmacological profile of MP-101, a novel non-racemic mixture of R- and S-dimiracetam with increased potency in rat models of cognition, depression and neuropathic pain. Cells 2022, 11, 4027. https://doi.org/10.3390/cells11244027