US experts to decide future of gene therapy

WASHINGTON: Experts were meeting on Friday to decide the future of gene therapy experiments after learning that two French “bubble boys” cured using gene therapy had developed cancer.

The specialists in cancer, gene therapy and bone marrow transplants who advise the U.S. Food and Drug Administration decided last October, after the first case was reported, that the benefits of gene therapy outweighed the risk of cancer.

But now that a second 3-year-old boy has developed leukemia, it is becoming clear that cancer is an inherent risk of the treatment, at least in this disease.

The meeting was being held 50 years to the day after Francis Crick and James Watson announced their discovery of the double helix structure of DNA.

While knowledge of genetics has in many cases transformed medicine, progress has often been slower than hoped. Gene therapy holds great promise, offering to cure disease by correcting faulty genes, but so far has produced few results.

The researchers at Necker Hospital in Paris had seen the first real success in gene therapy, curing 9 of 10 infant boys with a rare genetic disease called x-linked severe combined immunodeficiency (SCID). A 15-year-old boy was also treated but not helped by the gene therapy.

SCID patients are born without any working immune system. Without treatment, they once lived their short lives in sterile “bubbles” because any infection would kill them. A single genetic defect causes the syndrome.

It can be treated with bone marrow transplants, which are highly successful if done very early and with bone marrow from a relative whose tissue matches closely. But babies with no healthy matched relatives have fewer options.

The French researchers, led by Dr. Alain Fischer, used a retrovirus to carry normal copies of a gene to correct the defect in bone marrow stem cells, and then infused the cells back into the boys.

Random Effects Of Virus: But the virus they used inserts its genetic material randomly in cells. In the case of the two boys, and perhaps a third boy who has not developed cancer, the gene disrupted a sensitive area of the chromosome in a single cell.

The immune cell started out-of-control proliferation, eventually taking over all the other cells. This uncontrolled growth is the same as seen in leukemia.

The committee is trying to decide if there is a safer way to do the gene therapy, while still curing the children. Perhaps the viruses can be tinkered with to make them more controllable. Doctors may also be able to better choose the cells that are treated and put back into patients.

Other approaches dispense with viruses, using spheres of fat to deliver the DNA, or even using “naked” DNA.

Last October, the committee decided that gene therapy was the best hope for children who do not have a good bone marrow donor. They said the informed consent forms — which parents and patients read and sign before taking part in medical experiments — should warn clearly of the risk of cancer..

They also told investigators to carefully check patients to see if any of the viruses were integrating in the wrong place.

The boys were both treated soon after birth — one at the age of one month and one at three months. Both developed leukemia around age 3.

Experts believe it is possible Fischer’s team has had its remarkable success because they treat such young children. But it is also possible that babies are most susceptible to cancer, because their young immune systems are developing so rapidly.

Earlier this month the Recombinant Advisory Committee of the National Institutes of Health, which with the FDA regulates gene therapy, said gene therapy for SCID should for the time being be tried only in children who have not been cured by bone marrow transplants.

French gene therapy experiments are on hold while further tests are done on the patients. German authorities have put a hold on one experiment involving bone marrow cells, while Italy has halted all gene therapy for four months.

British authorities are deciding on a case-by-case basis whether to continue gene therapy experiments. —Reuters

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