Sangamo's Bet Against AIDS: Gene Therapy

Timothy Brown may be the only person cured of AIDS. Brown, who lives in San Francisco, in 2007 received a stem-cell transplant in Berlin that transferred genetic material to him from one of the up to 2 percent of humans with a natural immunity to the disease. He has been off treatment since then, and no traces of the AIDS virus have been found in his body, says his hematologist, Gero Hütter, now with the German Red Cross in Mannheim. His case has encouraged tiny Sangamo BioSciences (SGMO) to develop a new form of gene therapy that could offer others the same result.

While there's no guarantee Brown, 44, will remain virus-free, his case has spurred scientists to try to duplicate the result without a dangerous stem-cell transplant. Sangamo, a Richmond (Calif.) biotechnology company, will report data late this month on a gene therapy that's likely to be less risky. If the results are a success, and the method is eventually approved, it may generate $750 million a year in U.S. sales, says Liana Moussatos, a biotech analyst at Wedbush Securities. "It's high-risk, but definitely high-reward," she says. "If this is a cure for HIV that prevents or reduces the lifelong need for drugs, that's a huge accomplishment."

Sangamo's stock has more than doubled since July 6, when the company, with no products on the market, reported success of its gene therapy approach in mice in the journal Nature Biotechnology. One reason for the enthusiasm: The therapy, using a new technology that acts like biological scissors to cut into genes at precise points, may also treat other diseases, such as hemophilia, Parkinson's, and neuropathy, the nerve damage caused by diabetes, says Sangamo Chief Executive Officer Edward Lanphier. An approved treatment for neuropathy alone, which has no cure, may generate $6 billion a year, Moussatos says.

Sangamo is conducting two studies of its HIV therapy in 21 people. Both are in the first stage of testing usually required to win U.S. regulatory approval. Its preliminary data will be reported on Feb. 27 at a medical conference in Boston. Moussatos says that if the data are strong, Sangamo may attract partnerships with larger drugmakers that it will need to help finance larger trials.

There are 1.1 million Americans living with the AIDS-causing HIV virus, and 34 million are infected worldwide, according to the U.S. Centers for Disease Control and Prevention. Antiviral drugs, led by Atripla and Truvada, made by Gilead Sciences (GILD) and Bristol-Myers Squibb's (BMY) Reyataz, generated $15.1 billion in worldwide sales last year, according to industry researcher IMS Health.

AIDS first emerged in 1981 and, in the early years, killed most of those infected within a year of diagnosis. In 1996 doctors began combining three different families of drugs to overcome HIV's ability to become resistant. That extended lives of patients in North America and Europe by at least 13 years on average, according to a 2008 study. Still, the drugs aren't a cure, since the virus rebounds when their use stops. They are taken daily, often cause nausea, and can trigger kidney damage. They also need to be regularly adjusted as the virus mutates, gaining resistance in the body.

In the Sangamo process, doctors draw patients' blood and remove infection-fighting white blood cells. They are then modified using naturally occurring proteins called zinc fingers that cut into patients' DNA at selected points. Chopping the DNA in the middle of a gene called CCR5 eliminates a receptor that HIV uses to gain entry to cells. The modified cells are then returned to the patient through an infusion.

"This approach shows the most promise of any that I know of," says Jay A. Levy, a researcher at the University of California in San Francisco who helped identify HIV as the source of AIDS in 1984. "It's a terrific way of looking for a long-term functional cure for the virus."

One person who hopes it will prove effective is Matt Sharp, 54, an AIDS educator who was diagnosed in 1988 and today takes a daily regimen of three antivirals. He learned about the Sangamo trial a year ago and enrolled. Since last summer, when Sharp received an infusion of his own gene-modified T-cells, blood cells that help the immune system fight infection, the number of those cells has doubled, he says. "I'm just hoping I could get an infusion once a year that would keep HIV under control and I won't have to deal with the effects of taking medication."

CCR5 isn't a new target. The gene pathway was first noticed in the mid-1990s by scientists studying people immune to HIV infection. In these people, including the donor who contributed stem cells to Brown, the CCR5 gene is mutated and inactive, keeping the virus from gaining a foothold in the immune system. For most HIV patients, however, a stem-cell transplant is impractical and risky. It requires finding a donor with the CCR5 mutation and whose tissues and blood match the patient's—and carries about a 30 percent risk of death, says Levy.

That's too high a risk for most AIDS patients who have access to proven antiviral medicines. Brown, previously known in medical circles only as "the Berlin patient," was willing to take the chance because he also had developed a potentially fatal case of leukemia—a blood cancer that can also be treated by stem-cell transplants. When chemotherapy stopped controlling his leukemia, Brown and his doctors decided to find a donor with genetic characteristics that would allow treatment of both conditions simultaneously. Brown underwent two stem-cell transplants. Afterward he developed neurological problems and other side effects and spent a year in the hospital, at some points near death. He eventually recovered and was released in early 2009.

"If I hadn't survived, I kind of doubt that the work towards a cure would have gone this far," Brown says. Now he hopes scientists will be able to develop new therapies based on his treatment "so people can be cured of HIV without having to go through what I went through."

The bottom line: Sangamo BioSciences is testing a gene therapy for AIDS inspired by a cured patient. The first results come this month.

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