Year: 1999
Type: article
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.
DOI: 10.1172/jci5542
Authors: Yujing Liu, Ryuichi Wada, Hiromichi Kawai, Kazunori Sango, Chuxia Deng, Tadashi Tai, Michael P. McDonald, Kristlyn Araujo, Jacqueline N. Crawley, Uwe Bierfreund, Konrad Sandhoff, Kinuko Suzuki, Richard L. Proia
Institutions: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Tokyo Metropolitan Institute of Medical Science, National Institute of Mental Health, National Institute of Mental Health, National Institute of Mental Health, University of Bonn, University of North Carolina at Chapel Hill, Georgetown University Medical Center
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2130630186