Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1.

Abstract

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.

• Authors: Vera Fridman, Saranya Suriyanarayanan, Peter Novak, William David, Eric A Macklin, Diane McKenna-Yasek, Kailey Walsh, Razina Aziz-Bose, Anne Louise Oaklander, Robert Brown, Thorsten Hornemann, Florian Eichler
• Journal: Neurology (Neurology) Vol. 92 Issue 4 Pg. e359-e370 (01 22 2019) ISSN: 1526-632X [Electronic] United States
• PMID: 30626650 (Publication Type: Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

Chemical References

• 1-deoxysphingolipid
• Sphingolipids
• UCHL1 protein, human
• Serine
• SPTLC1 protein, human
• Serine C-Palmitoyltransferase
• Ubiquitin Thiolesterase

Topics

• Adolescent
• Adult
• Aged
• Double-Blind Method
• Female
• Follow-Up Studies
• Hereditary Sensory and Autonomic Neuropathies (drug therapy, etiology)
• Humans
• Male
• Middle Aged
• Neural Conduction (drug effects)
• Pain Measurement
• Serine (therapeutic use)
• Serine C-Palmitoyltransferase (genetics)
• Sphingolipids (metabolism)
• Surveys and Questionnaires
• Treatment Outcome
• Ubiquitin Thiolesterase (metabolism)
• Young Adult