Researchers at the Scripps Institute in San Diego have announced the successful reversal of a rare but fatal genetic disorder, cystinosis.
According to Dr. Stephanie Cherqui, assitant professor in the department of molecular and experimental medicine at Scripps, "After meeting the children who suffer from this disease, like an 18-year-old who has already had three kidney transplants, and the families who are desperately searching for help, our team is committed to moving toward a cure for cystinosis, a lysosomal storage disorder. This study is an important step toward that goal."
In the study, the Scripps scientists used adult stem cells derived from bone marrow to treat cystinosis in a mouse model. The results indicated an effective reversal of the cystine accumulation and consequent cascade of cell death that characterize the disease.
A natural byproduct of metabolism, cystine is usually discarded by the body in healthy individuals but is retained in cystinosis due to a genetic defect in the lysosomal cystine transporter. The subsequent accumulation of crystals in tissue throughout the body, especially in the kidneys and eyes, is especially damaging.
Although the disease is extremely rare – afflicting no more than 500 people in the U.S. and only 2,000 people worldwide – cystinosis is almost certainly fatal. Prior to stem cell technology, the only available treatment for the disease was cysteamine, which slows the progression of kidney degradation though it can neither reverse the overall progression of the disease nor can it prevent the inevitable end-stage kidney failure. Additionally, as Dr. Cherqui points out, "Cysteamine must be given every 6 hours, so children have to be woken up each night to take this drug, which has unpleasant side effects. So although there is a treatment, it is a difficult treatment that does not cure the disease."
With the use of autologous (in which the donor and recipient are the same person) adult stem cells derived from bone marrow, however, cystine levels dropped 80% in each organ, which is enough to prevent kidney dysfunction. Additionally, less cystine crystal deposition was found in the corneas, along with less bone demineralization and improved motor function. As Dr. Cherqui explains, "The results really surprised and encouraged us. 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."
As a doctoral student in France in 1998, Dr. Cherqui helped discover the gene involved in cystinosis. In 2000, she generated the mouse model of the disease that is now used to study cystinosis by specialists throughout the world.
The results of the study are expected to have far-reaching implications beyond cystinosis, with potential applications to other genetic diseases with systemic defects of a progressive nature.