UMass Chan Medical School Faculty Publications

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Department of Medicine

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Animals; Cells, Cultured; *Drug Discovery; Fibroblasts; High-Throughput Screening Assays; Humans; Mice; Muscular Atrophy, Spinal; RNA, Messenger; Small Molecule Libraries; Survival of Motor Neuron 1 Protein; Survival of Motor Neuron 2 Protein; Up-Regulation


Biochemistry | Molecular Biology | Nervous System Diseases


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.


SMA, SMN, SMN2, drug discovery, spinal muscular atrophy

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This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

DOI of Published Version



Cherry JJ, Osman EY, Evans MC, Choi S, Xing X, Cuny GD, Glicksman MA, Lorson CL, Androphy EJ. Enhancement of SMN protein levels in a mouse model of spinal muscular atrophy using novel drug-like compounds. EMBO Mol Med. 2013 Jul;5(7):1035-50. doi: 10.1002/emmm.201202305. Link to article on publisher's site

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EMBO molecular medicine

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