Date: 2015-04-21
Type of information: Collaboration agreement
Compound: small molecule antagonists of the P2X7 ligand-gated ion channel
Company: Affectis Pharmaceuticals (Germany) The Lead Discovery Center (LDC) (Germany) Charcot-Marie-Tooth Association (CMTA) (USA -IL)
Therapeutic area: Rare diseases - Genetic diseases - Neurological diseases
Type agreement: collaboration
Action mechanism: P2X7 antagonist/ion channel antagonist.
Disease: Charcot-Marie-Tooth (CMT) disease type 1A (CMT1A)
Details:
- • On April 21, 2015, the Charcot-Marie-Tooth Association (CMTA) announced that it has entered into a collaboration with Affectis Pharmaceuticals to evaluate the efficacy of advanced Affectis compounds in neurological and behavioral models of Charcot-Marie-Tooth disease type 1A (CMT1A). The goal of the collaboration is to evaluate the pharmacology of small molecule antagonists of the P2X7 ligand-gated ion channel that are being jointly developed by Affectis and the Lead Discovery Center GmbH (LDC). P2X7 is an ATP-gated ion channel which is essential for cellular calcium homeostasis, and for the maturation and release of pro-inflammatory cytokines, including interleukin-1beta (IL-1?). The collaboration’s aim is to demonstrate the potential of P2X7 antagonists that have high potency for the human form of P2X7 and are orally bioavailability in treating CMTA1. Use of such antagonists may impede the development of motor and sensory control defects associated with progression of the disease.
- Pre-clinical studies previously demonstrated a likely role for P2X7 over-activity in the pathogenesis of CMT1A (Nobbio et al. (2009) J. Biol.Chem. 284, 23146). An altered calcium homeostasis was observed in Schwann cells from rats that exhibit a CMT1A pathology due to the expression of extra copies of the pmp22 gene; this is hypothesized to lead to the disruption of myelination associated with the disease. The authors further showed that the changes in intracellular calcium coincided with overexpression of the P2X7 ligand-gated ion channel, and that its inhibition leads to myelin repair.
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