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Huntington's disease (HD)

p75 neurotrophin receptor (p75 NTR)

Mouse studies suggest inhibiting p75 NTR could help treat HD. In a mouse model of HD, expression of the two putative HD targets brain-derived neurotrophic factor (Bdnf) and its receptor, neurotrophic tyrosine kinase receptor 2 (Ntrk2; TrkB), were normal, but Bdnf-dependent synaptic potentiation was decreased compared with that in normal mice. In the HD mouse model, shRNA knockdown or peptide-mediated inhibition of the downstream TrkB target p75 Ntr restored Bdnf-dependent synaptic potentiation. Next steps include identifying selective small molecule antagonists of p75 NTR and identifying other potential targets in the pathway.
Sanofi has the p75 NTR antagonist SAR127963 in Phase I testing to treat shock/trauma.

SciBX 7(29); doi:10.1038/scibx.2014.871
Published online July 31, 2014

Unpatented; licensing status not applicable

Plotkin, J.L. et al. Neuron; published online July 2, 2014;
Contact: D. James Surmeier, Northwestern University, Chicago, Ill.