16 August 2012

The green light of gene therapy

Genes decide everything

Alexey Bondarev, "Correspondent" No. 31-2012
Published on the LIGABisnesInform portalA big medical revolution has taken place in Europe – the EU authorities for the first time allowed doctors to use gene therapy, that is, to take a broad step towards defeating cancer and AIDS.

"If writers Robert Sheckley, Philip K. Dick or Robert Heinlein had lived to 2012, they would have been happy to see their wildest dreams come true," says Martin Clark, an American physician and part–time big fan of fiction.

Moreover, Clark does not mean achievements in the field of gadget building or space exploration, although humanity can be proud of these successes. According to the doctor, the news that appeared in July about the decision of the European Medical Commission can make any skeptic believe that the pace of scientific and technological progress is irreversible.

The authorities of the United Europe, long famous for their bureaucracy, for the first time in history approved the use of gene therapy for the treatment of a hereditary disease. Clark calls this event epochal: it testifies to the victory of new thinking in medicine over the traditional one and to the revision of the attitude of official medicine to the classical norms of morality, which are rooted in religious foundations.

According to Clark, the norms of conventional morality are still strong in the United States, which hinders the development of medicine. He recalls with a grin the ban on embryonic stem cell research under Republican President George W. Bush, because of which American science was thrown back years compared to European science, and many outstanding scientists from the United States were looking for work abroad.

Conservative people believe that even under the pretext of saving human life, changing the human genetic code is an intervention in God's providence, explains American physician David Carradine. The decision of European regulators suggests that the Middle Ages in medicine are coming to an end, he says, at least in Europe.

The first steps in the field of gene therapy can be made by European medicine in the coming years. It remains to be hoped that the US authorities will come to their senses, Carradine believes.

So far, we are talking about the treatment of only one rare genetic disease, but if successful, gene therapy methods may become more widely used by the end of the decade, experts suggest. This means a real revolution in medicine, a revolution of such a scale that the classics of science fiction of the last century could only dream of, Clarke notes.

Gene therapy is based on the idea of replacing a defective section of human DNA with a new genetic material with a normal structure. Theoretically, this method can cure any serious congenital disease, Clark believes, and therefore save millions of lives.

The Great RevolutionAs a field for legal trials of gene therapy, European doctors chose the Burger-Greutz syndrome, that is, hereditary deficiency of lipoprotein lipase, or, more simply, lack of ability to digest fats.

This kind of disease is just an Everest for modern medicine, Clarke explains. The cause of the disease is damage to the gene structure (so in the text – VM) responsible for the breakdown of fats in the digestive tract. As a result, fats accumulate in the blood, which leads to acute pancreatitis and other serious ailments.

Until recently, it was possible to alleviate the condition of patients with Burger-Greutz syndrome only with the help of the strictest fat-free diet. However, in many cases it is ineffective, doctors say.

The Glybera drug, which the commission allowed to be tested on such patients, is the embodiment of the gene therapy method. The essence of the method is to use a virus that infects muscle tissue and thus introduces a copy of an intact gene into the body. As a result, the damaged sections of DNA are replaced by normal ones. Theoretically, after that, the disease caused by damage to DNA sites will be defeated.

"Patients with lipoprotein lipase deficiency are afraid to eat normal food because it can lead to acute and extremely painful inflammation of the pancreas, which often ends in hospitalization," explains Jorn Aldag, head of the pharmaceutical company UniQure, which developed the drug.

According to Aldag, the new drug is a unique treatment method that not only reduces the risk of inflammation, but also has a long-term beneficial effect on the patient's condition.

The Thorny pathSkeptics are in no hurry to take Aldag's words on faith.

In reality, gene therapy does not look as rosy as in theory. Tests of the method conducted before, as a rule, were unsuccessful. So, in 1999, the experiment was allowed in the USA for the first and last time. Then a group of doctors led by biologist James Wilson tried using gene therapy to cure a group of volunteer patients from hereditary liver disease. One of them, 18-year-old Jess Gelsinger, died 98 hours after the drug was administered.

"The patient's body reacted to the drug unpredictably," Wilson later recalled. – The subject quickly began to have inflammation, one by one the organs failed." As it turned out, Gelsinger had an individual intolerance to proteins that were used to transmit a virus designed to make changes in the patient's genetic code.

As a result, Wilson was banned from conducting clinical trials involving humans, and experiments with gene therapy in the United States are still not welcome.

A few years later, the image of gene therapy was slightly improved by the work of an American researcher Jean Bennett, a professor at the University of Pennsylvania. During her experiments, she was able to restore vision in one eye to nine-year-old Corey Haas, who was born with a hereditary visual defect. Haas was given an injection in the eye in the immediate vicinity of the retina, and the drug used was a set of artificially created viruses capable of penetrating cells and introducing their genes into them. The improvement became noticeable after two weeks. Now Haas sees with one eye – the one in which the injection was made.

According to Olga Zelenaya, a co-author of the work and an employee of the Philadelphia Children's Hospital, over the next two years of observations of Haas and other patients who took part in the experiments, no negative consequences were noticed.

"Bennett has made impressive progress," says Wilson. "This is science with a capital letter."

A contribution comparable to Bennett's success in the field of gene therapy was also made by French scientist Patrick Aubur from the National Scientific Medical Institute of France. Obur was able to cure two seven–year-old patients from adrenoleukodystrophy - a congenital disease in which a child's brain is gradually destroyed. This is due to a deficiency of hemocytoblasts – stem cells necessary for the formation of a protective sheath of nerve fibers.

Until now, it has been possible to defeat this disease only with the help of cell transplantation from a suitable donor, and this is a very expensive and complex procedure. Aubur tried a different method – genetic modification of the patient's own hemocytoblasts. Scientists took samples of stem cells from patients, infected them with therapeutic viruses carrying corrected sections of the genetic code, and returned these cells to the body again.

A modified human immunodeficiency virus was adopted as a basis, which retains the ability to infect cells, but, once in the body, loses the ability to reproduce. The virus was injected into two babies with an acute form of the disease. A year after the operation, their condition improved noticeably, and a brain scan confirmed that their nervous system was getting in order.

"Unlike other children suffering from this disease, our test subjects have already gone to school and live a normal life," says the scientist.

Aubur is convinced that gene therapy will soon work in full force. According to the doctor, it will help fight diseases such as hemophilia, Parkinson's disease and AIDS. In order for the victory march to begin, you just need to get permission from the authorities for large-scale experiments.

Glimmers of hope The victory over AIDS, of course, is still a rather vague prospect.

But, in addition to the experiments of Bennett and Aubur, as well as the European initiative to combat Burger-Greutz syndrome, scientists in different countries are ready to use gene therapy to solve topical issues of modern medicine at the first opportunity.

Experts from Cornell University suggest using gene therapy to combat smoking. A special gene will be injected into the patient's body with the help of a therapeutic virus that blocks the flow of nicotine into the brain (so in the text – VM). The smoker will stop enjoying nicotine, and therefore, there is a high probability that he will give up the bad habit.

According to Professor Ronald Crystal, who is leading the study, after obtaining the appropriate permits for experiments, it will take no more than five to seven years to develop a universal smoking cure. Kristel even believes that the authorities should make smoking vaccination mandatory in childhood in order to eliminate any chances of spreading the addiction in future generations.

Gene therapy will also be effective for the treatment of cancer. For example, scientists from the University of Illinois suggest treating skin cancer, and at the same time psoriasis with a lotion that changes the work of genes in damaged cells.

Dermatologists Chad Mirkin and Amy Peller have developed a unique technique consisting in the formation of spheres of proteins and RNA molecules around a gold nanoparticle. Such spheres 1000 times smaller than a human hair will be able to penetrate through the skin and affect the affected genes.

The first experiments on mice confirmed the effectiveness of the method. Mirkin even suggests that the method will eventually allow not only to fight cancer, but will also revolutionize cosmetology, since it will mean victory over wrinkles.

According to Clark, these are just flowers, and even the most optimistic scientists cannot imagine the main consequences of successful experiments in the field of gene therapy. "In theory, by getting a working method of delivering healthy sections of the genetic code into the body, we will be able to defeat absolutely any hereditary disease," says Clark. "This is a bigger revolution than the invention of penicillin or antibiotics."

Portal "Eternal youth" http://vechnayamolodost.ru16.08.2012

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