A German AIDS patient was able to stop drugs he had been taking for 10 years after getting a transplant of stem cells from a donor with a rare gene variant known to resist the deadly disease. The transplant also cured his leukemia, researchers reported.
The stem cell donor was among the 1 percent of Caucasians who have the variant gene that lacks a section known as CCR5 that helps the AIDS virus enter a cell, according to a report today in the New England Journal of Medicine. Doctors in Berlin hoped that putting the donor’s stem cells in the patient would rebuild his immune system and blood cells so they would lack the CCR5 piece.
The results of the experiment may point researchers to a new way of controlling the AIDS virus HIV that doesn’t force patients to take drugs for the rest of their lives. Scientists will now intensify their search for therapies that achieve the same effect, predicted Jay Levy, a University of California, San Francisco, AIDS researcher.
“I think this article is going to stimulate a lot of companies to put more emphasis on gene therapy,” Levy said yesterday in a telephone interview. He wasn’t involved in the research and wrote an editorial published today that accompanied the study.
One such trial sponsored by Sangamo Biosciences of Richmond, California, recently began at the University of Pennsylvania. It will test a gene therapy that aims to modify the immune cells in 12 patients infected with HIV so they lack the CCR5 receptor.
Reports about the successful treatment of the German patient presented at a medical meeting last year bolstered the company’s belief that they were on the right track, said Elizabeth Wolffe, a Sangamo spokeswoman.
“The fact that you could put back into the patient CCR5- deficient cells and have those cells work to clear the virus -- that gave us a lot of confidence,” she said in a telephone interview yesterday.
The 40-year-old patient described in today’s journal report had been treated in Germany with antiviral drugs for 10 years, since his HIV infection was diagnosed. In July 2006, he developed leukemia and was given chemotherapy in an effort to eradicate the cancer.
While the chemotherapy controlled the blood cancer, it also made him ill, causing liver and kidney failure, said Gero Hutter, a hematologist at Benjamin Franklin Hospital in Berlin who led his treatment and was co-author of the report. When doctors halted his antiviral drugs, his levels of the AIDS virus spiked until he resumed taking them after a few weeks.
After a few more months went by, his leukemia returned and doctors decided to try a stem cell transplant, a risky procedure that kills nearly a third of patients. They figured that as long as they were doing a transplant, they might as well look for a donor who didn’t have the key section of CCR5.
“Our thinking was that if we do this and replace his immune system with cells that are resistant to HIV, we can do two things at once” by stopping his leukemia and his HIV infection, Hutter said in a telephone interview yesterday.
Stem cells from bone marrow, which are also found in circulating blood, have the ability to form blood cells including the white blood cells that fight infection. These are the cells that are attacked by the virus, crippling patients’ immune systems.
Hutter and his colleagues scanned the genomes of 60 potential donors and found one who lacked the CCR5 section. The day after they transfused the donor’s stem cells into the patient, they stopped the antiviral therapy that had suppressed his HIV levels.
“There’s been no rebound of HIV,” Hutter said. “Now, two years after transplantation, we can’t find any HIV in this patient.”
Hutter also said that gene therapy experiments that try to achieve the same goal of inactivating CCR5 hold promise. While the stem cell transplant is too risky to try in most AIDS patients, there may be some who are so sick that it would be worth the danger. First, he said, it should be tried in another patient with both AIDS and leukemia.
When people missing this gene fragment get infected with HIV, they don’t usually develop AIDS symptoms or produce large amounts of the virus.
One drug on the market, Pfizer’s Selzentry, is designed to block the CCR5 receptor so the AIDS virus can’t enter healthy cells. While the drug helps some patients, it must be used with other medications and doesn’t keep the virus from sneaking in