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Stem Cells Virtually Halt Rare Genetic Disease in Mouse Model

Scientists studying the rare and deadly genetic disease cystinosis, have shown that transplantation of adult bone marrow stem cells appears to virtually halt the disease in a mouse model. Cystine is a byproduct of the lysosomal breakdown of cellular components the body no longer needs. Normally, cystine is shunted out of cells, but in cystinosis a gene defect of the lysosomal cystine transporter causes cystine to build up, forming crystals that are especially damaging to the kidneys and eyes. The only available drug to treat cystinosis, cysteamine, while slowing the progression of kidney degradation, does not prevent it, and end-stage kidney failure is inevitable. "Cysteamine must be given every six hours, so children have to be woken up each night to take this drug, which has unpleasant side effects, and many others to treat various symptoms," said Dr. Stephanie Cherqui, the senior author of the study. "So although there is treatment, it is difficult treatment that does not cure the disease." In the study, the research team used bone marrow stem cell transplantation to address symptoms of cystinosis in a mouse model. The procedure virtually halted the cystine accumulation responsible for the disease and the cascade of cell death that follows. The researchers found that transplanted bone marrow stem cells carrying the normal lysosomal cystine transporter gene abundantly engrafted into every tissue of the experimental mice. This led to an average drop in cystine levels of about 80 percent in every organ. In addition to preventing kidney dysfunction, there was less deposition of cystine crystals in the cornea, less bone demineralization, and an improvement in motor function. "The results really surprised and encouraged us," said Dr. Cherqui. "Because the defect is present in every cell of the body, we did not expect a bone marrow stem cell transplant to be so widespread and effective." The work of Dr. Cherqui and her colleagues may have wider applications for other genetic diseases, providing proof of principle that adult stem cell transplants may be successful in humans for genetic diseases with systemic defects, especially those of a progressive nature. The study is reported in the September 17 issue of Blood. [Press release] [Blood abstract]