Correctional work

Gene therapy has been talked about for more than twenty years. But from the cradle she began to emerge only now

Until recently, nine-year-old American Cory Haas spent almost all his time at home. Now it is impossible to take him off the street: he plays baseball and rides a bicycle all day long. Most of his life, Haas was blind: he was born with a hereditary visual defect, a form of Leber's amaurosis. This severe disease occurs due to the mutation of a single gene - RPE65. Conventional medicines are powerless here. Haas was helped by the unusual. With the consent of the parents, the child took part in a scientific experiment. Employees of the Philadelphia Children's Hospital introduced a normally working version of the gene into his body. Haas's disease began to pass literally before our eyes.

Corey Haas is not alone. In total, University of Pennsylvania professor Jean Bennett has twelve such patients. In November, the prestigious medical journal Lancet published her article detailing the experiment. Not only scientists, but also officials from the US Department of Health are eyeing Bennett's results. Now the researcher has a good chance to get official approval of her gene therapy method, which no one has yet been able to do before her.

Scientists have been talking about such therapy for 25 years. Its effectiveness has been repeatedly confirmed in animals. But with the practical application of these methods in humans, things were not so rosy. Until now, only participants in very rare experiments could receive a life-saving genetic drug. More recently, the situation has begun to change.

VISIBLE EFFECT

Now Corey Haas can only see with one eye. The other one still barely works. These are the conditions of clinical trials - doctors do not want to take risks. “Patients are literally begging us to give them a second shot,” says Bennett co-author Olga Zelenaya of Philadelphia Children's Hospital. What doctors call an injection is more like a surgical operation. A thin needle penetrates the patient's eye and the drug is released in close proximity to the retina.

Bennett's genetic drug is a suspension of adeno-associated viruses. They are able to penetrate human cells and transfer their genes there. And along with any others introduced into the virus by scientists. Patients received at least 15 billion of these viral particles. Each contained a "healthy" copy of the RPE65 gene. “Over two years of observation, our operation did not cause any noticeable complications in patients,” says Zelenaya. But there is a positive effect.

Vision began to recover in all patients after two weeks. Bennett expects that patients will not have to do a second injection soon. Four years ago, a similar method of treatment was tested by a group of French scientists on sick dogs. Scientists did not bring the matter to experiments on humans, but in animals everything is still in order with vision.

Now the leadership in this area belongs to the Bennett group. With the paper published, scientists have already begun planning the next phase of clinical trials. This time, twelve volunteers are not enough. According to the rules of the US Food and Drug Administration (FDA), not tens, but hundreds of people should participate in the next phase of experiments.

It is possible that the FDA will greenlight gene therapy for the first time. Bennett's work is highly appreciated by her colleagues. For example, the Russian biologist Fedor Urnov. He develops genetic treatments for diseases at the American company Sangamo BioSciences. And this does not prevent him from praising someone else's result: "Finally, after 25 years of research, someone managed to create a procedure with which you can really treat people." Another scientist joins Urnov - the famous American biologist James Wilson. “This is real Science with a capital letter,” Wilson enthuses. "Bennett has made impressive progress."

The fact that this kind of treatment can not necessarily be successful, Wilson knows better than anyone else. In 1999, he directed one of the first officially approved trials of a genetic drug. Its results are often told as an edification to students of the Faculty of Biology at Moscow State University. In theory, the drug developed by scientists was supposed to save volunteers from hereditary liver disease. In fact, the virus carrying the therapeutic gene killed one of the volunteers, 18-year-old Jesse Gelsinger. “The patient's body responded to the administration of the drug in an unpredictable way,” Wilson recalls. "The subject rapidly developed inflammation and began to fail organs." Jesse Gelsinger died 98 hours after the injection. Now Wilson knows exactly why: the patient had an individual intolerance to the proteins of the virus used for therapy. A few days after Gelsinger's death, the whole world knew about this story. Wilson's study was canceled, and he himself was deprived of the right to conduct clinical trials on humans for 11 years. The ban expires in 2010.

NERVOUS WORK

Along with Gelsinger, gene therapy almost died. The once fashionable trend fell into disgrace. The FDA froze all such experiments for a long time. And ten years later, very few scientists risk doing such experiments. Last year, Bennett was able to compete only with Patrick Aubourg from the National Medical Institute of France.

His article, published in the November issue of the journal Science, made a lot of noise. In his work, Aubur combined two new methods of treating people at once - gene and cell therapy. He managed to cure two seven-year-old patients from adrenoleukodystrophy. In people suffering from this disease, the brain begins to collapse even in early childhood. This is how the congenital defect of hemocytoblasts, the stem cells involved in the formation of the protective sheath of nerve fibers, makes itself felt. Now this disease can be cured only by cell transplantation from a suitable donor. This is if it can be found.

Obur and his colleagues proposed an alternative - to genetically modify the patient's own hemocytoblasts. The researchers took samples of stem cells from patients, infected them with viruses carrying therapeutic genes, and returned them to the body. They used a modified and safe form of the human immunodeficiency virus. This virus retains the ability to infect cells very effectively, but can no longer multiply in the body. A year after this operation, the condition of the patients improved markedly. A brain scan of both children on a tomograph confirmed that their nervous system is gradually getting in order.

“With such a diagnosis, a person usually quickly becomes incapacitated, and our patients have gone to school and live quite a normal life,” Obur rejoices. The scientist shared with Newsweek plans for the future: in the near future, he and his colleagues will begin the second phase of testing, already on 10-20 patients. Aubur is optimistic. According to him, gene therapy will soon work in full force. With its help, it will be possible to treat hemophilia, Parkinson's disease and even AIDS.

Of course, such research will require huge investments. How much their past experiments cost, Bennett and Aubur flatly refuse to say. An approximate estimate of the minimum cost is given by Fedor Urnov. According to him, the development of a new method of treatment requires a minimum of $3 million. Creating your own viral gene transfer system is another $100,000 to $1 million. Clinical trials will entail new expenses. The first two phases of the experiments could easily cost another $2 million. And there are no guarantees that the idea will justify itself in the end.

The high price of gene therapy scares skeptics no less than the story of Jesse Gelsinger. For all its effectiveness, gene therapy is neither a vaccine nor an antibiotic. It is possible that this method will never be affordable for the average patient and, on the contrary, will only increase the gap between the quality of life of representatives of different social groups.

Other scientists criticize gene therapy from much more prosaic positions. For example, Jonathan Kimmelman, a biophysicist from McGill University, believes that you should not blindly believe the results of clinical trials. According to him, such experiments have one serious drawback - so far, people who are literally on the verge of death are allowed to participate in the testing of gene preparations. In this situation, it is difficult for experimenters to be objective. Negative side effects from therapy can easily be attributed to the general condition of the patient. Given the cost of such research, this temptation is not easy to resist.