Affiliations: [a] Department of Biological Chemistry and Pharmacology, The Ohio State University Wexner Medical Center, Columbus, OH, USA
| [b] Center for Applied Clinical Genomics, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA
| [c] Center for Pediatric Research, Nemours Biomedical Research, Nemours Alfred I. duPont Hospital for Children, Wilmington, DE, USA
| [d] Department of Pediatrics, Thomas Jefferson University, Philadelphia, PA, USA
| [e] Department of Biological Sciences, University of Delaware, Newark, DE, USA
Correspondence:
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Correspondence to: Matthew E. R. Butchbach, Ph.D., Nemours Biomedical Research, Alfred I. duPont Hospital for Children, 240 Rockland Center One, 1600 Rockland Road, Wilmington, DE 19803, USA. Tel.: +1 302 298 7366; Fax: +1 302 651 6539; E-mail: butchbach@nemoursresearch.org.
Abstract: Spinal muscular atrophy (SMA) is an early-onset motor neuron disease that leads to loss of muscle function. Butyrate (BA)-based compounds markedly improve the survival and motor phenotype of SMA mice. In this study, we examine the protective effects of the BA prodrug pivaloyloxymethyl butyrate (AN9) on the survival of SMNΔ7 SMA mice. Oral administration of AN9 beginning at PND04 almost doubled the average lifespan of SMNΔ7 SMA mice. AN9 treatment also increased the growth rate of SMNΔ7 SMA mice when compared to vehicle-treated SMNΔ7 SMA mice. In conclusion, BA prodrugs like AN9 have ameliorative effects on SMNΔ7 SMA mice.
Keywords: Motor neuron disease, spinal muscular atrophy, preclinical drug trial, neonatal mouse, AN9
