title: The debut of a rational treatment  for an inherited neuropathy?
abstract: 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.
authors: Department of Neurology, The Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104-6077, USA. sscherer@mail.med.upenn.edu
authors: Steven S
authors: SS
authors: Scherer
mesh_terms: D000818:Animals; D005260:Female; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000188:drug therapy*; D006801:Humans; D008055:Lipids; D008297:Male; D009498:Neurotoxins / Q000096:biosynthesis*; D012694:Serine / Q000627:therapeutic use*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000096:biosynthesis
chemical_list: D008055:Lipids; D009498:Neurotoxins; D012694:Serine; D013110:Sphingosine; C408363:spisulosine