Gene Therapy Trial Approved For Rare Anemia

Currently, the best survival hope for Fanconi patients is a bone marrow transplant from a donor with a perfect tissue match. However, for most patients, a suitable donor cannot be found in time.

"In people with Fanconi anemia, the bone marrow fails. It's a failure state like liver failure or heart failure," says Dr. Christopher E. Walsh, assistant professor of medicine at UNC-CH School of Medicine and clinical director of the university's Gene Therapy Center. "The bone marrow failure associated with this anemia leads to severe reductions in the numbers of circulating blood cells, including red cells, all types of white cells and platelets, which are crucial to clotting."

According to Walsh, the majority of individuals with Fanconi anemia are unaware they have the disease. "By and large, most patients come to medical attention because they have something wrong with their blood cell counts," he says. However, he notes that in some people with low cell counts, certain physical characteristics may raise medical suspicion of Fanconi. These can include short stature, finger deformities, and hyperpigmentation of the skin -- so-called "café au lait" spots.

The phase I clinical trial will test the safety and feasibility of correcting the blood disorder by transferring a cloned corrective gene called FAA into a patient's very primitive bone marrow cells - "progenitor" stem cells from which all blood cells are formed. These progenitor cells, which have been removed from bone marrow for the gene transfer, are then re-infused into the patient. Compelling evidence from prior laboratory studies indicate that the corrective gene, when packaged with a retrovirus, can enter the cell nucleus and enable formation of the millions of healthy blood cells that are needed every day.

Fanconi anemia affects an estimated 2,000 to 3,000 people in the United States and Europe. Given these relatively small numbers, Walsh says he hopes to enroll at least 10 patients for the trial.

"Fanconi anemia is a perfect candidate disease for the use of gene therapy," Walsh says. "What we learn from here can be applied to other disorders involving a single gene."