In a freezer in La Jolla, CA, is a bank of frozen skin cells collected from patients with a rare and devastating genetic disorder called Lesch-Nyhan disease. Children born with the disease have a genetic error that causes them to produce too much uric acid, which builds up in their tissue. They also suffer major neurological problems in roughly the same part of the brain stricken by Parkinson’s disease, resulting in motor and cognitive problems. “No one understands why a defect in this gene leads to a defect in the brain,” says Theodore Friedmann, a pediatrician and geneticist at the University of California, San Diego, who has been studying the disease for almost 40 years.
About two years ago, Friedmann, an expert in gene therapy, began to consider how stem cells could help his patients. Embryonic stem cells have two valuable properties: under the right conditions, they can regenerate themselves – dividing to create identical new cells – and they are pluripotent, meaning they can develop into almost any type of cell in the body. That magnificent pliancy captivates scientists like Friedmann, who dream of the day they can take stem cells, coax them to become new brain or liver cells, and transplant them into patients with Parkinson’s disease or organ failure.
Scientists have already shown that in animals, stem cells can help treat heart disease, spinal-cord injury, and sickle cell anemia, among other things. Rats with damaged spinal cords regained some mobility after injections of neural precursor cells made from embryonic stem cells. Stem cells transplanted into rats’ heart tissue can help heal damaged heart muscles.
But before similar therapies can be tested in people, scientists will need to resolve the problem of immune rejection. Transplanted stem cells, which are now derived from discarded embryos, are genetically different from their recipients; like donor kidneys, they thus carry the risk of provoking an immune response. That means that even the most advanced treatments are still years away from clinical use. Therapeutic cloning is one way to make stem cells suitable for transplant, since it yields cells that share their recipients’ DNA.
Theoretically, cloned stem cells could help Friedmann’s patients; scientists could fix the genetic defect in the cells before implanting them. The prospect of such revolutionary treatment is what has most captivated both the public and the media. But Friedmann and Snyder are focusing on an application that could have much broader implications – and is closer at hand. Instead of using the cells as a form of therapy themselves, the researchers plan to use them to study Lesch-Nyhan disease and test new treatments. Experts say this type of application could dramatically improve our understanding of how any disease with a genetic component unfolds at the cellular level. “You could make a stem cell line that has ALS or Parkinson’s, using DNA from a patient that really has the symptoms,” says Snyder.
Scientists could prod the cells to develop into the type of cells damaged by a disease, such as dopamine neurons in Parkinson’s, and study the intricate progression of the disease from its earliest stirrings to its final cellular death knell. Because the cells would be genetically identical to the patient’s DNA, they would undergo many of the same molecular changes that underlie the patient’s disease.