Scripps Institute researchers have transplanted bone marrow stem cells in a treatment that successfully addressed the 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.
Cystine is a byproduct of the break down of cellular components the body no longer needs in the cell's "housekeeping" organelles, called lysosomes. Normally, cystine is shunted out of cells, but in cystinosis a gene defect of the lysosomal cystine transporter causes it to build up, forming crystals that are especially damaging to the kidneys and eyes.
In the new study, 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 principal investigator Stephanie Cherqui, assistant professor in the Department of Molecular and Experimental Medicine. Cherqui, who as a doctoral student in France in 1998 helped discover the gene involved in cystinosis, added, "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."
Cherqui, who generated the mouse model in 2000 that is currently used to study cystinosis, says that adult bone marrow stem cell therapy is particularly well suited as a potential treatment for cystinosis because these cells target all types of tissues. In addition, stem cells reside in the bone marrow for the duration of a patient's life, becoming active as needed, a particular benefit for a progressive disease like cystinosis.
This is another example of the possibility of stem cell treatments in wider applications for genetic diseases and again suggests proof of principle that adult stem cell transplant treatments may be successful in humans for genetic diseases with systemic defects, especially those of a progressive nature.
About Cystinosis:
While cystinosis is rare—affecting an estimated 500 people in the United States and 2,000 worldwide—it is devastating. Three types of cystinosis have been described based on the age at diagnosis and the amount of cystine in cells: infantile onset, adolescent onset, and adult onset. Children as young as six months can begin to suffer renal dysfunction, which grows progressively worse with time. Other symptoms include diabetes, muscular disease, neurological dysfunction, and retinopathy. Infantile onset is the most common, as well as the most severe, form of the disease.
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," Cherqui says. "So although there is treatment, it is difficult treatment that does not cure the disease."
Adapted from the Scripps Research Institute announcement through EurekAlert.
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