No effective treatments exist for individuals with hereditary neuropathies. On the basis of recent progress in understanding the cause of one such disorder, hereditary sensory and autonomic neuropathy type 1 (HSAN1), K. Garofalo et al. provide initial promising results for a mechanism-based therapy for this rare disease: dietary supplementation with L-serine (J. Clin. Invest. doi:10.1172/JCI57549).
HSAN1 is caused by mutations in genes that encode subunits of serine palmitoyltransferase, which catalyzes the first step in sphingolipid biosynthesis. These mutations loosen the substrate specificity of the enzyme, allowing it to use alanine or glycine rather than serine. This change in substrate results in the production of deoxysphingolipids, which may be neurotoxic. Proceeding from this mechanistic framework, the researchers hypothesized that increasing serine levels might be beneficial. Indeed, dietary supplementation with L-serine in a mouse model of HSAN1 decreased plasma deoxysphingolipid levels and decreased neuropathic symptoms. In 14 individuals with HSAN1, L-serine dietary supplementation also reduced plasma deoxysphingolipid levels.
In view of the short 10-week course of L-serine supplementation, neurological symptoms were not examined in the treated individuals with HSAN1. A larger and longer-term clinical trial will now be needed to test the safety and efficacy of this therapy.
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Basson, M. Serine to the rescue. Nat Med 17, 1566 (2011). https://doi.org/10.1038/nm.2607