A genetic model of substrate deprivation therapy for a glycosphingolipid storage disorder

Yujing Liu, Ryuichi Wada, Hiromichi Kawai, Kazunori Sango, Chuxia Deng, Tadashi Tai, Michael P. McDonald, Kristlyn Araujo, Jacqueline Crawley, Uwe Bierfreund, Konrad Sandhoff, Kinuko Suzuki, Richard L. Proia

Research output: Contribution to journalArticlepeer-review

145 Scopus citations


Inherited defects in the degradation of glycosphingolipids (GSLs) cause a group of severe diseases known as GSL storage disorders. There are currently no effective treatments for the majority of these disorders. We have explored a new treatment paradigm, substrate deprivation therapy, by constructing a genetic model in mice. Sandhoff's disease mice, which abnormally accumulate GSLs, were bred with mice that were blocked in their synthesis of GSLs. The mice with simultaneous defects in GSL synthesis and degradation no longer accumulated GSLs, had improved neurologic function, and had a much longer life span. However, these mice eventually developed a late- onset neurologic disease because of accumulation of another class of substrate, oligosaccharides. The results support the validity of the substrate deprivation therapy and also highlight some limitations.

Original languageEnglish (US)
Pages (from-to)497-505
Number of pages9
JournalJournal of Clinical Investigation
Issue number4
StatePublished - Feb 1999
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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