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A Ten-Year Check-Up Shows Gene Therapy Patients are Alive and Well

By Veronique Greenwood
Aug 25, 2011 11:29 PMNov 19, 2019 9:13 PM


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What's the News: Medicine in the age of genes overflows with daring new techniques and treatments, from personalized chemotherapy to prenatal genetic testing, each heralded as a game-changer. But rarely do we get an assessment of a treatment's long-term good, which is why recent papers following up on one of the most controversial genetic treatments, gene therapy, are making waves: though one patient developed leukemia from the treatment, 13 of 16 kids treated with gene therapy for a severe immune disorder at least 9 years ago have been cured, adding to the sense that the field is on its way to recovery from early setbacks. The Backstory:

  • Gene therapy involves correcting errors in cells' genetic code. In the case of some of these children, who had no functioning immune system due to X-linked SCID---severe combined immunodeficiency, or "bubble boy" syndrome---bone marrow transplants had been the only way to effectively treat the disease (for kids with ADA-SCID, caused by a missing enzyme, weekly enzyme injections are also possible, but bone marrow transplants are the only way to eliminate it). But marrow transplants require a matching donor, like a sibling, and when one isn't available, the odds of success with an unmatched donor aren't great.

  • Removing faulty immune cells from the kids, fixing the genetic problem with a virus specially designed to snip and swap DNA, and reintroducing the modified cells into the body seemed like a promising way to treat the disease. Scientists began trials in children with SCID in the 1990s.

  • But the field was shaken first in 1999, when a participant in a gene therapy trial for another disease died, and in 2001 when some of the children treated for SCID with gene therapy began to come down with leukemia. To their horror, researchers found that the kids had developed the disease because the DNA-inserting virus had disturbed parts of the genome near cancer-causing genes. Trials were stopped, and the field went dormant, becoming a classic example in biotechnology textbooks of the dangers of reaching too far too fast.

  • But in recent years, scientists' work to rehabilitate gene therapy has begun to pay off---it's cured hemophilia and color-blindness in animals and a type of leukemia in people. Researchers have developed screening procedures and new techniques that safeguard against the kinds of errors that let to the disastrous setbacks of the 90s. And now, these new follow-up studies indicate that the original goal of gene therapy, curing people of genetic disease for the long term, was indeed achieved.

The Results:

  • The scientists report on two groups of patients with two different forms of SCID, both treated at least 9 years ago with gene therapy. Papers in 2000 and 2002 documented the groups at the outset.

  • Of the X-linked SCID patients, one did develop leukemia, although he is now in remission. He and the nine other patients quickly developed more healthy immune systems and have been able to attend normal school without fear of lethal infections.

  • Of the ADA-SCID patients, four of the six built up enough of an immune system that they were able to stop their enzyme-replacement therapy. The other two had to stay on the therapy, as the fixed immune cells didn't take.

The Future Holds:

  • These success rates are pretty phenomenal, especially given how deadly untreated SCID is and how complex gene therapy can be. The lead researcher told Nature News that with these data, especially for kids with X-linked SCID without a matching bone marrow donor, gene therapy is now the best treatment out there.

  • More studies of gene therapy in children with SCID and other genetic diseases are no doubt on the horizon, and with the new techniques developed since these kids were first treated, children in the new trials will hopefully have lower rates of complications.

References: H. B. Gaspar, et al. Long-term persistence of a polyclonal T cell repertoire after gene therapy for X-linked severe combined immunodeficiency.

Sci. Transl. Med. 3, 97ra79 (2011). H. B. Gaspar, et al. Hematopoietic stem cell gene therapy for adenosine deaminase–deficient severe combined immunodeficiency leads to long-term immunological recovery and metabolic correction

. Sci. Transl. Med. 3, 97ra80 (2011).

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