Human trial shows promise

Health Progress, Sep/Oct 2001

Type A hemophilia is a genetic condition in which a single mutation robs the body of its ability to manufacture a protein known as factor VIII. Without this protein, patients bleed profusely from minor cuts and bruises and even suffer spontaneous hemorrhages within joints. Only injections of purified factor VIII allow their blood to clot and wounds to heal.

Science News reported on a study in the New England Journal of Medicine in which skin cells were harvested from six people with hemophilia A. The cells were impregnated with bacterial DNA that contained the gene for factor VIII production, then cultured for injection into the test subjects. Three subjects were administered 100 million cells, and the other three were given 400 million.

Tests administered over the course of a year indicated that all three members of the high-dose group and one member of the low-dose group had elevated levels of factor VIII in their blood. Two of the patients for whom the therapy had the strongest effect did not report any need for clotting factor injections for 10 months, beginning shortly after the treatment.

Clotting factor levels, though elevated, were still far below normal levels. Other hematologists question whether the 2 percent to 4 percent of normal factor VIII levels is in fact a therapeutic amount, or if the lack of a control group can account for any possible placebo effect. They question whether any of the subjects failed to take clotting-factor concentrates because they expected to feel better. Further research may better indicate exactly how much the treatment helps, and if the duration of benefits could be extended.

Hematology researchers are nevertheless enthusiastic about the implications of the therapy, which marks the first human trial of gene therapy for the disease. Hemophilia A has been an inviting subject for recombinant gene techniques, due to its origin in a single mutation. Delivering a viable copy of the gene in question continues to be a difficult task for researchers, though certain developments for both hemophilia A and B show promise.