Kathy High’s father once thought she’d make a better scientist than doctor, she says, “because it was his impression that I panicked in the face of danger.” That’s an overstatement, High claims, and even as her colleagues down the street face an FDA-imposed shut-down, still in effect as TR went to press, she isn’t beating a retreat. She has a couple of reasons to stand her ground. For one thing, she is using a safer gene-therapy delivery system, or “vector,” than the one that killed Gelsinger. And the disease she’s trying to cure-hemophilia-is more common and less complicated to treat genetically than Gelsinger’s.
High works in partnership with Alameda, Calif.-based Avigen and Stanford geneticist Mark Kay, and they have plenty of competition. Two other biotech firms, Transkaryotic Therapies (TKT) of Cambridge, Mass., and Emeryville, Calif.’s Chiron, have also launched clinical trials to test their own versions of hemophilia gene therapy. At least four other biotech companies have shown interest in joining the race.
Gene therapists are looking to hemophilia as the disease whose cure will begin to justify the billions lavished on research, attract new private investment, fulfill the hype and dispel the stigma of failure. “That kind of success will have a big impact,” says Joe Glorioso, director of the University of Pittsburgh’s gene-therapy center, “at least in the investment community, on whether we should support this kind of biotechnology or not.” Beyond redeeming the field, a cure for hemophilia would be a late but just reward for a patient population that has suffered great pain over the last 20 years.
Hemophilia is an inherited bleeding disorder that afflicts males almost exclusively. It’s caused when the gene for either of two protein “clotting factors,” factor VIII or factor IX, is damaged or missing. Most people with hemophilia-about 17,000 in the United States alone-treat their bleeds by injecting concentrated “factor” made from blood products or by genetic engineering. During the early 1980s, blood products contaminated with HIV decimated the hemophilia community. “Sixty percent of our families have had somebody die or have AIDS from transfused material,” says New York’s Mt. Sinai Medical Center hemophilia specialist Lou Aledort.
John Lanzon, a 52-year-old medical technologist in Detroit, is typical of his generation of hemophilia sufferers. Lanzon walks with a limp, the legacy of dual knee-replacement surgery, and his elbows resemble gnarled driftwood. That’s because people with hemophilia do not bleed uncontrollably from cuts but instead tend to bleed into their joints, which suffer long-term damage, partly from enzymes that break down the blood. Contaminated factor gave Lanzon hepatitis B and C, as well as HIV, though he has yet to develop AIDS. Better blood-screening and heat-treatment practices, along with genetic engineering, have made today’s treatments safe, but hardly ideal. “Factor will stop the bleeding,” Lanzon says, “but it’s not going to do a thing for the inflammation and the pain.”
Because clotting factors are tremendously expensive (more than $1,000 a dose), most people with hemophilia, including Lanzon, treat themselves only after a bleed starts. Preventive treatments are a painful burden for children. Adding a good copy of the defective gene, if it works, would put a constant stream of clotting factor into the blood and eliminate bleeds altogether. Rather than just serving as a palliative, it would be a cure. “A single treatment that would keep the boys from having pain or permanent joint disability,” says Children’s Hospital of Philadelphia hematologist Katie Manno, the doctor in charge of administering High’s experimental treatment to patients, “would be perfect.”