Enhancement of SMN protein levels in a mouse model of spinal muscular atrophy using novel drug‐like compounds
Year: 2013
Type: article
Abstract: Spinal muscular atrophy (SMA) is a neurodegenerative disease that causes progressive muscle weakness, which primarily targets proximal muscles. About 95% of SMA cases are caused by the loss of both copies of the SMN1 gene. SMN2 is a nearly identical copy of SMN1, which expresses much less functional SMN protein. SMN2 is unable to fully compensate for the loss of SMN1 in motor neurons but does provide an excellent target for therapeutic intervention. Increased expression of functional full-length SMN protein from the endogenous SMN2 gene should lessen disease severity. We have developed and implemented a new high-throughput screening assay to identify small molecules that increase the expression of full-length SMN from a SMN2 reporter gene. Here, we characterize two novel compounds that increased SMN protein levels in both reporter cells and SMA fibroblasts and show that one increases lifespan, motor function, and SMN protein levels in a severe mouse model of SMA.
Source: EMBO Molecular Medicine
Authors: Jonathan J. Cherry, Erkan Y. Osman, Matthew C. Evans, Sungwoon Choi, Xuechao Xing, Gregory D. Cuny, Marcie A. Glicksman, Christian L. Lorson, Elliot J. Androphy
Language: English
Subfield: Genetics
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $7,990
Awards: Testing Compounds that Increase SMN levels for Efficacy in Mouse Models of SMA, Optimization of drug-like compounds for treatment of spinal muscular atrophy, Cooperative lead development program for treatment of spinal muscular atrophy, High Throughput Screen for Compounds to Treat Papillomavirus Induced Cancers
OpenAlex ID: W1935644875