nad a22 4500 569274567 20190725055513.0 cr unu---uuuuu 190725e20190122xx s 000 0 eng 10.5167/uzh-171623 doi 10.1212/WNL.0000000000006811 doi (ZORA)oai:www.zora.uzh.ch:171623 610 ddc 540 ddc 30626650 pmid Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1 [Elektronische Daten] [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] openAccess eu-repo 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, = 0.03), with evidence of continued improvement in the second year of treatment (-0.77, 95% CI -1.67 to 0.13, = 0.09). Concomitantly, deoxysphinganine levels dropped in l-serine-treated but not placebo-treated participants (59% decrease vs 11% increase; < 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. Institute of Clinical Chemistry zora Fridman Vera joint author Suriyanarayanan Saranya joint author Novak Peter joint author David William joint author Macklin Eric A. joint author McKenna-Yasek Diane joint author Walsh Kailey joint author Aziz-Bose Razina joint author Oaklander Anne Louise joint author Brown Robert joint author Hornemann Thorsten joint author Eichler Florian joint author Neurology 92(4):e359-e370 https://www.zora.uzh.ch/id/eprint/171623/1/NEUROLOGY2018889709.pdf text/html WWW-Backlink auf das Repository 1 Journal Article PeerReviewed zora ZORA 856 40 https://www.zora.uzh.ch/id/eprint/171623/1/NEUROLOGY2018889709.pdf text/html WWW-Backlink auf das Repository ZORA 700 1- Fridman Vera joint author ZORA 700 1- Suriyanarayanan Saranya joint author ZORA 700 1- Novak Peter joint author ZORA 700 1- David William joint author ZORA 700 1- Macklin Eric A. joint author ZORA 700 1- McKenna-Yasek Diane joint author ZORA 700 1- Walsh Kailey joint author ZORA 700 1- Aziz-Bose Razina joint author ZORA 700 1- Oaklander Anne Louise joint author ZORA 700 1- Brown Robert joint author ZORA 700 1- Hornemann Thorsten joint author ZORA 700 1- Eichler Florian joint author ZORA 773 0- Neurology 92(4):e359-e370 BK010053 XK010053 XK010000 ZORA ZORA ZORA Journal Article openAccess