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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Copyright © 2019 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.
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, Vera; Suriyanarayanan, Saranya; Novak, Peter; David, William; Macklin, Eric A.; McKenna-Yasek, Diane; Walsh, Kailey; Aziz-Bose, Razina; Oaklander, Anne Louise; Brown, Robert H. Jr.; Hornemann, Thorsten; and Eichler, Florian, "Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1" (2019). Open Access Articles. 3714.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.