Gene Therapy for Patients with Factor IX Deficiency

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Beyond Blood

Finding a cure for hemophilia has proved more difficult than people initially thought. However, over the last year there has been tremendous progress. In December 2011, promising early results of a clinical trial of gene therapy from the United Kingdom on severe FIX deficiency were published (Nathwani et al., New England Journal of Medicine). In this study, all six men who were treated had responses with factor IX levels of 2 to 11 percent. Four of the men were able to discontinue prophylaxis.

In December 2012, CHOP opened a gene therapy clinical trial for patients older than 18 years of age, with factor IX levels equal to or less than 2 percent. This is still an early phase trial, investigating the safety and optimal dose. This is similar to the study from the U.K. (though not exactly the same).

How does it work?

Led by Katherine High, Ph.D., an adult hematologist and world-renowned investigator, scientists at CHOP have genetically engineered a non-disease causing virus, adeno-associated virus, to carry the DNA of the human factor IX gene. This is called the gene therapy vector. When infused into a vein, the vector goes to the liver (where normal factor IX is produced), and enters a liver cell. Then that cell starts producing factor IX.

What are the potential side effects?

One of the main concerns is that the human immune system will think the gene therapy vector is foreign and develop an immune response to try to get rid of it. This immune response has been seen in prior gene therapy trials, and it can be treated with a short course of prednisone, a mild immunosuppressive. Since this is new therapy, all of the risks are unknown. This is why it must be studied carefully in a clinical trial, and also why this therapy is not yet available to children.

What about gene therapy for factor VIII deficiency?

Currently, the only clinical trials for gene therapy in hemophilia are for FIX deficiency. This is because the gene for factor IX is much smaller than factor VIII. It has been more challenging to develop vectors for factor VIII. However, scientists are busy developing gene therapy vectors for Hemophilia A patients, and early studies are promising.

If you have questions or may want to participate in the clinical trial at CHOP, please call Dr. Raffini, at 267-426-5029.