Identification of novel compounds that increase SMN protein levels using an improved SMN2 reporter cell assay

Jonathan J. Cherry, Matthew C. Evans, Jake Ni, Gregory D. Cuny, Marcie A. Glicksman, Elliot J. Androphy

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Spinal muscular atrophy (SMA) is a neurodegenerative disorder that is characterized by progressive loss of motor neuron function. It is caused by the homozygous loss of the SMN1 (survival of motor neuron 1) gene and a decrease in full-length SMN protein. SMN2 is a nearly identical homolog of SMN1 that, due to alternative splicing, expresses predominantly truncated SMN protein. SMN2 represents an enticing therapeutic target. Increasing expression of full-length SMN from the SMN2 gene might represent a treatment for SMA. We describe a newly designed cell-based reporter assay that faithfully and reproducibly measures full-length SMN expression from the SMN2 gene. This reporter can detect increases of SMN protein by an array of compounds previously shown to regulate SMN2 expression and by the overexpression of proteins that modulate SMN2 splicing. It also can be used to evaluate changes at both the transcriptional and splicing level. This assay can be a valuable tool for the identification of novel compounds that increase SMN2 protein levels and the optimization of compounds already known to modulate SMN2 expression. We present here preliminary data from a high-throughput screen using this assay to identify novel compounds that increase expression of SMN2.

Original languageEnglish (US)
Pages (from-to)481-495
Number of pages15
JournalJournal of Biomolecular Screening
Issue number4
StatePublished - Apr 2012


  • cell-based assay
  • high-content screening
  • HTS
  • SMN1
  • SMN2
  • spinal muscular atrophy
  • survival of motor neuron

ASJC Scopus subject areas

  • Analytical Chemistry
  • Drug Discovery
  • Pharmacology
  • Biochemistry
  • Molecular Medicine
  • Biotechnology

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