Gene Therapy Used to Treat Hemophilia in Dogs

5:59 PM EST; February 24, 2000; CNN; Washington, D.C. (Reuters) -- Researchers said Wednesday they had used gene therapy to treat hemophilia in dogs, and said a single treatment had continued to work for ten months in one of the animals. They said the next step would be to try the treatment, which stimulates activity of one of the genes controlling blood clotting, in humans.

Lili Wang and Inder Verma of the Salk Institute in La Jolla, California, tested their approach on four dogs that had naturally developed hemophilia B, a blood-clotting disorder, in just the way humans do. Hemophilia B, which affects about one in 50,000 males, is caused by a defect in the gene for Factor IX, a blood clotting protein. Because a single gene is involved in hemophilia, it is a key target of scientists testing gene therapies.

With gene therapy, doctors usually try to introduce a new, healthy gene into the patient's body. Wang, now at the University of Pennsylvania's Institute for Gene Therapy, tried a different approach. Writing in the journal Molecular Therapy, published by the American Society for Gene Therapy, she said that she introduced two genes into the dogs instead -- one a promoter gene telling Factor IX to turn on, and one a post-transcriptional factor that would control production of the protein. Wang's team used an adeno-associated virus to carry the genes into cells, infusing it directly into the dogs' livers.

After a single infusion, the dogs were all expressing Factor IX, meaning their bodies were producing it. But only the dog that got the highest dose had enough to prevent the spontaneous bleeding that marks hemophilia and makes it so dangerous. "No spontaneous bleeding has been observed in this dog," Wang said in a telephone interview. It is now ten months since the dogs were first treated.

She said the dog expresses about five percent of the normal levels of Factor IX, but said this would be enough in a human patient to consider that patient well-treated. Currently, human hemophilia patients must receive regular injections of Factor IX, or Factor VIII if they have the more common hemophilia A.

"This study helps establish both the safety and the efficacy of recombinant adeno-associated virus for liver transfer of genes related to hemophilia, and suggests strongly that this approach could work in humans afflicted with the disease," the journal, edited by Verma, said in a statement.

Gene therapy has been under scrutiny since the death last year of an 18-year-old patient at th University of Pennsylvania. Several centers have suspended or slowed down their gene therapy programs while they review their procedures and government regulators examine the issue. But earlier this week Beth Israel Deaconess Medical Center in Boston said its researchers had resumed a trial involving 12 patients with hemophilia.

Alameda, California-based Avigen, Inc. is testing another gene therapy approach for hemophilia B in humans. Its Factor IX gene is injected into the muscles of patients and even in very small doses, in a trial meant to show only that the treatment is safe, it has seen evidence the new genes are working.