Chemical genetics and orphan genetic diseases

Chem Biol. 2005 Oct;12(10):1063-73. doi: 10.1016/j.chembiol.2005.09.005.


Many orphan diseases have been identified that individually affect small numbers of patients but cumulatively affect approximately 6%-10% of the European and United States populations. Human genetics has become increasingly effective at identifying genetic defects underlying such orphan genetic diseases, but little progress has been made toward understanding the causal molecular pathologies and creating targeted therapies. Chemical genetics, positioned at the interface of chemistry and genetics, can be used for elucidation of molecular mechanisms underlying diseases and for drug discovery. This review discusses recent advances in chemical genetics and how small-molecule tools can be used to study and ultimately treat orphan genetic diseases. We focus here on a case study involving spinal muscular atrophy, a pediatric neurodegenerative disease caused by homozygous deletion of the SMN1 (survival of motor neuron 1) gene.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Drug Design
  • Drug Industry / trends*
  • Humans
  • Models, Molecular
  • Muscular Atrophy, Spinal / drug therapy
  • Muscular Atrophy, Spinal / genetics
  • Muscular Atrophy, Spinal / pathology
  • Rare Diseases / drug therapy*
  • Rare Diseases / genetics*
  • Rare Diseases / pathology