Clinical trial of L-Carnitine and valproic acid in spinal muscular atrophy type I.

Barbara Hero, Kathryn J Swoboda, Brunhilde Wirth, Ai Sakonju, Bernard Lasalle, Charles B Scott, Thomas W Prior, Louise R Simard, Bakri Elsheikh, Edward C Smith, Guy D'Anjou, Kristin J Krosschell, Jürgen-Christoph Von Kleist-Retzow, Priya S Kishnani, Gyula Acsadi, Mary K Schroth, Thomas O Crawford, Sandra P Reyna, Ren Zhe Zhang, Sarah D Simeone, Elise L Townsend, John T Kissel

Journal: Muscle & nerve 2019;57(2):193-199

PMID: 28833236

Abstract

INTRODUCTION

The aim of this study was to determine the safety and therapeutic potential of L-carnitine and valproic acid (VPA) in infants with spinal muscular atrophy (SMA).

METHODS

Our investigation was an open-label phase 2 multicenter trial of L-carnitine and VPA in infants with SMA type I with retrospective comparison to an untreated, matched cohort. Primary outcomes were: safety and adverse events; secondary outcomes were survival, time to death/>16 hours/day of ventilator support; motor outcomes; and maximum ulnar compound motor action potential amplitude.

RESULTS

A total of 245 AEs were observed in 35 of the 37 treated subjects (95%). Respiratory events accounted for 49% of all adverse events, resulting in 14 deaths. Survival was not significantly different between treated and untreated cohorts.

DISCUSSION

This trial provides evidence that, in infants with SMA type I, L-carnitine/VPA is ineffective at altering survival. The substantial proportion of infants reaching end-points within 6 months of enrollment underscores the urgent need for pre-symptomatic treatment in SMA type I. Muscle Nerve 57: 193-199, 2018.

© 2017 Wiley Periodicals, Inc.

Address: Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.; Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.; Department of Physical Therapy, Institute of Health Professions, Massachusetts General Hospital, Boston, Massachusetts, USA.; Department of Neurology, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Simches 5-240, Boston, Massachusetts, 02114, USA.; Department of Neurology, University of Utah, Salt Lake City, Utah, USA.; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.; Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.; Connecticut Children's Medical Center, Hartford, Connecticut, USA.; Department of Pediatrics, Duke University, Durham, North Carolina, USA.; Department of Pediatrics, Hospital of the University of Cologne, Cologne, Germany.; Department of Pediatrics, Saint-Justine Hospital, Montreal, Quebec, Canada.; Biochemistry and Medical Genetics, University of Manitoba, Winnepeg, Manitoba, Canada.; Department of Molecular Pathology, The Ohio State University, Columbus, Ohio, USA.; CBS Squared, Inc, Fort Washington, Pennsylvania, USA.; Department of Bioinformatics, University of Utah, Salt Lake City, Utah, USA.; Department of Neurology, State University of New York, Syracuse, New York.; Institute of Human Genetics, Center for Molecular Medicine Cologne, Center for Rare Diseases Cologne.; Institute of Genetics, University of Cologne, Cologne, Germany.

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