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Gene therapy appears to work for hemophilia B patients

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After 20 years of frequent setbacks in the gene therapy field, scientists have shown--in a handful of patients with hemophilia B--that gene therapy can work for a long period of time.

They proved this in a small, proof of concept trial involving 6 male patients with the rare bleeding disorder, which mostly affects men and is caused when the Factor IX gene is defective. To reverse it, they infused the adeno-associated virus-8 into patients' veins, which travels to the liver, carrying genes to generate correct copies of Factor IX. Four out of the 6 patients responded so well that they stopped the treatment after a single injection, The New York Times' Nicholas Wade reported Dec. 10. Two others needed more, though infrequent injections, Wade wrote.

Such an advance is early-stage, but the hope is that it could someday replace the use of frequent treatments with manufactured Factor IX, which can cost hundreds of thousands of dollars annually, both Wade and Reuters' Deena Beasley note in separate articles.

The University College London Cancer Institute and St. Jude Children's Research Hospital in Memphis, TN, produced the latest research, which The New England Journal of Medicine reported online Dec. 10. Coming next: a larger dosing trial involving 20 additional patients. Scientists are exploring a similar approach to treat hemophilia A, which affects substantially more people. We're hopeful that the trials continue successfully but gene therapy, unfortunately, has demonstrated enormous risks for side effects.

For 20 years, scientists have been driven by the desire to treat rare diseases or replace the use of expensive drugs that produce side effects and limited benefits, but have had few successes on even this limited scale, the Times noted. One Arizona teenager died in a gene therapy experiment about 12 years ago. Two other French boys were cured of their rare immune disorder in 2002, but the treatment gave them leukemia, Beasley reported.

So how did the treatment work more successfully this time? The Times' Wade terms the advance as representing the culmination of "several minor improvements developed over many years by different groups of researchers." For example, an earlier effort in 2006, pioneered by Dr. Katherine High of The Children's Hospital of Philadelphia, helped a patient produce his own Factor IX for about 10 weeks before it stopped. She told Wade that scientists made the latest iteration of the delivery virus more efficient. She also zeroed in on another innovation the latest researchers tried that worked: steroids to suppress the patients' immune systems so they don't attack the delivery virus (one of many unfortunate gene therapy side effects in the past). With more consistent success, this time we may actually see a gene therapy reach the marketplace.

Still, success in the trial wasn't universal. Wade reports that the patients produced their own Factor IX protein for up to 22 months, though one patient's level of Factor IX has declined to 1% of the normal amount, making him vulnerable to the disease once again.

- here's Nicholas Wade's NYT story
- here's Deena Beasley's Reuters piece
- read the NEJM coverage
- check out the NEJM editorial

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