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 Mcdonald, Kristlyn Araujo, Jacqueline N. Crawley, Uwe Bierfreund, Konrad Sandhoff, Kinuko Suzuki, Richard L. Proia

Research output: Contribution to journalArticle

140 Citations (Scopus)

Abstract

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
Volume103
Issue number4
DOIs
StatePublished - Feb 15 1999

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Glycosphingolipids
Genetic Models
Sandhoff Disease
Therapeutics
Nervous System Diseases
Oligosaccharides
Reproducibility of Results
Nervous System

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Liu, Y., Wada, R., Kawai, H., Sango, K., Deng, C., Tai, T., ... Proia, R. L. (1999). A genetic model of substrate deprivation therapy for a glycosphingolipid storage disorder. Journal of Clinical Investigation, 103(4), 497-505. https://doi.org/10.1172/JCI5542

A genetic model of substrate deprivation therapy for a glycosphingolipid storage disorder. / Liu, Yujing; Wada, Ryuichi; Kawai, Hiromichi; Sango, Kazunori; Deng, Chuxia; Tai, Tadashi; Mcdonald, Michael; Araujo, Kristlyn; Crawley, Jacqueline N.; Bierfreund, Uwe; Sandhoff, Konrad; Suzuki, Kinuko; Proia, Richard L.

In: Journal of Clinical Investigation, Vol. 103, No. 4, 15.02.1999, p. 497-505.

Research output: Contribution to journalArticle

Liu, Y, Wada, R, Kawai, H, Sango, K, Deng, C, Tai, T, Mcdonald, M, Araujo, K, Crawley, JN, Bierfreund, U, Sandhoff, K, Suzuki, K & Proia, RL 1999, 'A genetic model of substrate deprivation therapy for a glycosphingolipid storage disorder', Journal of Clinical Investigation, vol. 103, no. 4, pp. 497-505. https://doi.org/10.1172/JCI5542
Liu, Yujing ; Wada, Ryuichi ; Kawai, Hiromichi ; Sango, Kazunori ; Deng, Chuxia ; Tai, Tadashi ; Mcdonald, Michael ; Araujo, Kristlyn ; Crawley, Jacqueline N. ; Bierfreund, Uwe ; Sandhoff, Konrad ; Suzuki, Kinuko ; Proia, Richard L. / A genetic model of substrate deprivation therapy for a glycosphingolipid storage disorder. In: Journal of Clinical Investigation. 1999 ; Vol. 103, No. 4. pp. 497-505.
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