Nature Communications (Apr 2022)

CDP-ribitol prodrug treatment ameliorates ISPD-deficient muscular dystrophy mouse model

  • Hideki Tokuoka,
  • Rieko Imae,
  • Hitomi Nakashima,
  • Hiroshi Manya,
  • Chiaki Masuda,
  • Shunsuke Hoshino,
  • Kazuhiro Kobayashi,
  • Dirk J. Lefeber,
  • Riki Matsumoto,
  • Takashi Okada,
  • Tamao Endo,
  • Motoi Kanagawa,
  • Tatsushi Toda

DOI
https://doi.org/10.1038/s41467-022-29473-4
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 13

Abstract

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Ribitol-phospate modification is essential for the function of α-dystroglycan, and mutations in ISPD, an enzyme that synthesizes the the ribitol-phosphate donor CDP-ribitol, cause muscular dystrophy. Here, the authors show that recovery of CDP-ribitol levels, either via AAV-mediated gene therapy or prodrug treatment, rescues dystroglycan function and pathology in a mouse model.