Addex Therapeutics won an $835,000 grant from the Michael J. Fox Foundation for Parkinson’s Research (MJFF) to fund the discovery and development of tyrosine receptor kinase B (TrkB)-positive allosteric modulators (PAMs) for treating Parkinson’s disease.

TrkB is a high-affinity receptor of neurotrophins, including brain-derived neurotrophic factor (BDNF). The receptor mediates the effects of BDNF in supporting neuronal survival and the growth and differentiation of new neurons and synapses. Addex says allosteric modulation has demonstrated the potential to enhance TrkB activation, and the firm has applied its proprietary allosteric modulation screening platform to identify several series of novel small-molecule TrkB PAMs. The MJFF grant will support development of preclinical candidates for testing in in vivo models. 

Robert Lutjens, head of discovery at Addex, said the Swiss firm's initial discoveries represent an important step toward developing a potential drug candidate. “The Addex TrkB PAM program is an excellent demonstration of the broad potential of Addex proprietary biology and chemistry capabilities for identifying and optimizing allosteric modulators across diverse classes of drug targets.”

“Supporting research that can potentially protect the brain cells affected by Parkinson's disease is an important priority area at MJFF,” added Marco Baptista, Ph.D., MJFF director of research programs. “The development of such a therapy would be life changing for the millions living with or at risk for this disease. The Addex allosteric modulator discovery platform has identified promising TrkB PAM compounds toward that goal, and we look forward to its continued progress.”

Addex is focused on developing orally available small-molecule allosteric modulators for neurological disorders. Lead compound dipraglurant (mGluR5 negative allosteric modulator of NAM) is poised to start in Phase III development, also with MJFF funding, for treating Parkinson’s disease levodopa-induced dyskinesia. In October 2016, Addex confirmed plans to start a separate Phase IIa study with dipraglurant in focal cervical dystonia. Addex’s second clinical program, ADX71149 (mGluR2 positive allosteric modulator or PAM), is being developed in collaboration with Janssen Pharmaceuticals for treating epilepsy. 

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