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Muscle Nerve. 2018 Feb;57(2):193-199. doi: 10.1002/mus.25776. Epub 2017 Sep 18.

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

Author information

1
Department of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
2
Department of Neurology, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.
3
Department of Physical Therapy, Institute of Health Professions, Massachusetts General Hospital, Boston, Massachusetts, USA.
4
Department of Neurology, Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, Simches 5-240, Boston, Massachusetts, 02114, USA.
5
Department of Neurology, University of Utah, Salt Lake City, Utah, USA.
6
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
7
Department of Pediatrics, School of Medicine and Public Health, University of Wisconsin, Madison, Wisconsin, USA.
8
Connecticut Children's Medical Center, Hartford, Connecticut, USA.
9
Department of Pediatrics, Duke University, Durham, North Carolina, USA.
10
Department of Pediatrics, Hospital of the University of Cologne, Cologne, Germany.
11
Department of Pediatrics, Saint-Justine Hospital, Montreal, Quebec, Canada.
12
Biochemistry and Medical Genetics, University of Manitoba, Winnepeg, Manitoba, Canada.
13
Department of Molecular Pathology, The Ohio State University, Columbus, Ohio, USA.
14
CBS Squared, Inc, Fort Washington, Pennsylvania, USA.
15
Department of Bioinformatics, University of Utah, Salt Lake City, Utah, USA.
16
Department of Neurology, State University of New York, Syracuse, New York.
17
Institute of Human Genetics, Center for Molecular Medicine Cologne, Center for Rare Diseases Cologne.
18
Institute of Genetics, University of Cologne, Cologne, Germany.

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.

KEYWORDS:

L-carnitine; clinical trials; infants; natural history; spinal muscular atrophy type I; valproic acid

PMID:
28833236
DOI:
10.1002/mus.25776

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