Department of Neurology
Amino Acids, Peptides, and Proteins | Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Nervous System Diseases | Neurology | Therapeutics
OBJECTIVE: To evaluate the safety and efficacy of l-serine in humans with hereditary sensory autonomic neuropathy type I (HSAN1).
METHODS: In this randomized, placebo-controlled, parallel-group trial with open-label extension, patients aged 18-70 years with symptomatic HSAN1 were randomized to l-serine (400 mg/kg/day) or placebo for 1 year. All participants received l-serine during the second year. The primary outcome measure was the Charcot-Marie-Tooth Neuropathy Score version 2 (CMTNS). Secondary outcomes included plasma sphingolipid levels, epidermal nerve fiber density, electrophysiologic measurements, patient-reported measures, and adverse events.
RESULTS: Between August 2013 and April 2014, we enrolled and randomized 18 participants, 16 of whom completed the study. After 1 year, the l-serine group experienced improvement in CMTNS relative to the placebo group (-1.5 units, 95% CI -2.8 to -0.1, p = 0.03), with evidence of continued improvement in the second year of treatment (-0.77, 95% CI -1.67 to 0.13, p = 0.09). Concomitantly, deoxysphinganine levels dropped in l-serine-treated but not placebo-treated participants (59% decrease vs 11% increase; p < 0.001). There were no serious adverse effects related to l-serine.
CONCLUSION: High-dose oral l-serine supplementation appears safe in patients with HSAN1 and is potentially effective at slowing disease progression.
CLINICALTRIALSGOV IDENTIFIER: NCT01733407.
CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that high-dose oral l-serine supplementation significantly slows disease progression in patients with HSAN1.
L-serine, hereditary sensory autonomic neuropathy type I, HSAN1
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DOI of Published Version
Neurology. 2019 Jan 22;92(4):e359-e370. doi: 10.1212/WNL.0000000000006811. Epub 2019 Jan 9. Link to article on publisher's site
Fridman V, Suriyanarayanan S, Novak P, David W, Macklin EA, McKenna-Yasek D, Walsh K, Aziz-Bose R, Oaklander AL, Brown RH, Hornemann T, Eichler F. (2019). Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1. Open Access Articles. https://doi.org/10.1212/WNL.0000000000006811. Retrieved from https://escholarship.umassmed.edu/oapubs/3714
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.