4-aminopyridine reverses ataxia and cerebellar firing deficiency in a mouse model of spinocerebellar ataxia type 6

Sci Rep. 2016 Jul 6;6:29489. doi: 10.1038/srep29489.


Spinocerebellar ataxia type 6 (SCA6) is a devastating midlife-onset autosomal dominant motor control disease with no known treatment. Using a hyper-expanded polyglutamine (84Q) knock-in mouse, we found that cerebellar Purkinje cell firing precision was degraded in heterozygous (SCA6(84Q/+)) mice at 19 months when motor deficits are observed. Similar alterations in firing precision and motor control were observed at disease onset at 7 months in homozygous (SCA6(84Q/84Q)) mice, as well as a reduction in firing rate. We further found that chronic administration of the FDA-approved drug 4-aminopyridine (4-AP), which targets potassium channels, alleviated motor coordination deficits and restored cerebellar Purkinje cell firing precision to wildtype (WT) levels in SCA6(84Q/84Q) mice both in acute slices and in vivo. These results provide a novel therapeutic approach for treating ataxic symptoms associated with SCA6.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Aminopyridine / chemistry*
  • Animals
  • Cerebellum / drug effects*
  • Cerebellum / metabolism
  • Disease Models, Animal
  • Electrophysiology
  • Female
  • Heterozygote
  • Homozygote
  • Male
  • Mice
  • Mice, Transgenic
  • Motor Activity
  • Potassium Channels / metabolism
  • Purkinje Cells / metabolism
  • Spinocerebellar Ataxias / drug therapy
  • Spinocerebellar Ataxias / genetics*
  • Spinocerebellar Ataxias / metabolism


  • Potassium Channels
  • 4-Aminopyridine