Gene Therapy for Bleeding Disorder Has Potential For Cancer Treatment

Glanzmann's thrombasthenia is a rare inherited bleeding disorder found at a higher frequency among Iraqi Jews, French gypsies, and individuals of Arabic descent. It is marked by episodes of bleeding in the skull and in the digestive tract.

The disease is normally treated by transfusions of platelets, the cells that form blood clots. But many patients with the disease become unable to tolerate the transfusions. Hence the need to develop a better method of treatment.

A researcher at the Medical College of Wisconsin has used gene therapy to successfully correct a defect in the cells of individuals with Glanzmann's thrombasthenia. The strategy used in the laboratory research could one day be used to treat other disorders as well, says David A. Wilcox, PhD, Assistant Professor of Pediatrics and Associate Investigator at the Blood Research Institute.

Dr. Wilcox and colleagues enabled platelets from two patients with Glanzmann's thrombasthenia to stick together to properly form blood clots.

The researchers used a genetically inactivated mouse leukemia virus into which they inserted correctly functioning copies of the defective gene responsible for the disease. The altered virus was put into culture dishes containing bone marrow (parent) cells which make platelets.

"We put the virus in their food, and it binds to the cells and gets itself in," Dr. Wilcox explains.

The corrected cells formed blood clots when tested in the lab. A key feature of the research was having the healthy gene work only in the cells that need it. The way the scientists did this was to use a promoter, the gene's on-switch that allows the protein to be made only in the right cells.

"If you have a protein made in a cell where it is not normally made, that could lead to trouble. If you expressed a protein that helps platelets stick together in white blood cells or red cells that could make those cells stick together that don't normally stick together," says Dr. Wilcox.

Eventually, Dr. Wilcox hopes, this technique could be used to deliver drugs used in cancer therapy or be used to protect healthy cells from the side effects of chemotherapy.

Currently, however, he is focusing on applying the technique to lab animals. He is working with researcher Richard Hynes of MIT on mice with Glanzmann's thrombasthenia. Positive results in laboratory animals could lead to tests in people. Dr. Wilcox, however, can't say when that would be.

  The research is reported in the June 15, 2000, issue of Blood , and was conducted in collaboration with scientists from the University of North Carolina, Duke University, Mt. Sinai Medical School in New York, John Hopkins University, and Nexell Therapeutics, Inc.

MCW Health News presents up-to-date information on patient care and medical research by the physicians of the Medical College of Wisconsin.