The debut of a rational treatment for an inherited neuropathy?

J Clin Invest. 2011 Dec;121(12):4624-7. doi: 10.1172/JCI60511.


Hereditary neuropathies are common neurological conditions characterized by progressive loss of motor and/or sensory function. There are no effective treatments. Among the many causes of hereditary neuropathies are dominant mutations in serine palmitoyltransferase, long chain base subunit 1 (SPTLC1), which cause hereditary sensory and autonomic neuropathy type 1 (HSAN1). By incorporating L-alanine in place of L-serine, the mutant HSAN1–associated serine palmitoyltransferase generates deoxysphingolipids, which are thought to be neurotoxic. In this issue of the JCI, Garofalo and colleagues report that oral L-serine reverses the accumulation of deoxysphingolipids in humans with HSAN1 and in a transgenic mouse model. As oral L-serine reduces the severity of neuropathy in the mouse model of HSAN1, these data suggest a rational candidate therapy for this devastating condition.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Comment

MeSH terms

  • Animals
  • Female
  • Hereditary Sensory and Autonomic Neuropathies / drug therapy*
  • Humans
  • Lipids
  • Male
  • Neurotoxins / biosynthesis*
  • Serine / therapeutic use*
  • Sphingosine / analogs & derivatives*
  • Sphingosine / biosynthesis


  • Lipids
  • Neurotoxins
  • Serine
  • Sphingosine
  • spisulosine