vasoactive-intestinal-peptide and Muscular-Atrophy--Spinal

Spinal Muscular Atrophy (SMA) is one of the most common inherited causes of infant death and is caused by the loss of functional survival motor neuron (SMN) protein due to mutations or deletion in the SMN1 gene. One of the treatment strategies for SMA is to induce the expression of the protein from the homologous SMN2 gene, a rescuing paralog for SMA.. Here we demonstrate the promise of pharmacological modulation of SMN2 gene by BAY 55-9837, an agonist of the vasoactive intestinal peptide receptor 2 (VPAC2), a member of G protein coupled receptor family. Treatment with BAY 55-9837 lead to induction of SMN protein levels via activation of MAPK14 or p38 pathway in vitro. Importantly, BAY 55-9837 also ameliorated disease phenotype in severe SMA mouse models.. Our findings suggest the VPAC2 pathway is a potential SMA therapeutic target.

Topics: Animals; Disease Models, Animal; Mice; Muscular Atrophy, Spinal; Peptide Fragments; Receptors, Vasoactive Intestinal Peptide, Type II; Survival of Motor Neuron 1 Protein; Vasoactive Intestinal Peptide