Research

Gene therapy will be attempted to prevent Alzheimer's disease.

No one knows for sure what causes the disease.Alzheimer's But one fact about this disease has gained almost irrefutable status. Depending on which version of the APOE gene you inherit, the risk of brain disease may be two times lower than the average - or 12 times higher. APOE is sometimes called the “forgetfulness gene”, and it has three versions: 2, 3, and 4. Version 2 reduces the risk to humans; 3 - average; 4 - increases the risk radically.

The risk is so great that doctors avoid checking the status of APOE, because a bad result can upset a person - and nothing can be done about it. There is no cure, and the genes cannot be changed.

Or can it?

Can Alzheimer's be cured genetically?

While it is impossible. But doctors from New York have been saying that, starting in May, they will begin testing a new gene therapy in which people with the most unfortunate APOE genes will be given a huge dose of the risk reducing version.

If it helps slow slow exhaustionbrain disease to people who already have Alzheimer's, ultimately this will lead to the possibility of preventing the disease. The clinical trials led by Ronald Crystal from Weill Cornell Medicine in Manhattan represent a new tactic against dementia, as well as a new twist on gene therapy. Most of the efforts to replace genes that rely on viruses that carry DNA instructions into human cells are aimed at eliminating rare diseases, such as hemophilia, by replacing one defective gene.

But common diseases have no suchsingle causes, so gene therapy has never been particularly promising. The trade group Alliance for Regenerative Medicine claims that currently no gene therapy is being performed on Alzheimer's patients.

"It seems that the path to clinical trialsit will be long in public, but there is an urgent need for any treatment, ”says Kiran Musunuru, a professor at the University of Pennsylvania School of Medicine. He studies genetic methods for treating cardiovascular diseases and says that the experiment planned in New York represents a new category of gene therapy, the purpose of which is not to cure, but to reduce the risk of a future disease in healthy people.

Crystal says his plan also bypassesside of the discussion about the true cause of Alzheimer's disease, which has become a field of miracles with a multi-billion dollar turnover, in which both pharmaceutical companies and patients lose. In January, Roche stopped two large studies of antibodies that were supposed to clarify the properties of beta-amyloid plaques, the latest theory that claimed that these plaques around neurons lead to Alzheimer's.

"There are many in the area who firmly believe thatamyloid is to blame, ”says Crystal. Others believe that another protein is to blame - the tau - whose tangles were found in dying neurons. “The answer is likely to be hard to find. The approach we have chosen ignores all this and considers the situation from a genetic point of view. ”

At the same time, the Crystal team relies on the 25-year-oldopening. In the 1990s, scientists from Duke University were looking for proteins that could be attached to amyloid plaques. And they found apolipoprotein-e, which is encoded by the APOE gene. By sequencing this gene in 121 patients, they found that a separate version - APOE4 - was inexplicably distributed among those suffering from this disease.

The function of this gene is still not fully understood.(he plays a role in cholesterol and fat transport), but his risk factor status remains daunting. According to the Alzheimer's Association, about 65% of people with Alzheimer's disease have at least one copy of a dangerous gene. For people born with two high-risk copies, one from each parent, dementia becomes almost guaranteed if they live long enough.

However, some people inherit one 4 and one 2, low-risk version of the gene. These people have a closer to average risk, which suggests that the protective version of the gene compensates for the risky one.

This is the effect that Weill Cornell doctors will try.to copy. Currently, the center is looking for people with two copies of a high-risk gene that has already lost memory or even acquired Alzheimer's. According to Krystal, in about a month, the first volunteers will receive an infusion into the spinal cord from a billion viruses carrying gene 2.

Based on monkey tests, Crystalexpects viruses to spread the "happy gene" in cells throughout the patient's brain. Mice were treated the same way, and rodents accumulated less amyloid in the brain.

This strategy, according to the researcher, is notdepends on knowing everything about what really causes the disease. “In Alzheimer's, we are attracted by the obvious genetic epidemiology,” he says. “So the strategy is, can we redeem the brain in E2? We have the infrastructure for this, so we thought, why not? This solves the problem of the disease mechanism. ”

"The concept is rational," adds Crystal. “Whether it will work with a person is another question.”

The New York study will be preliminary. Crystal says that his team needs to determine if the added gene is functioning at the level at which it can be detected. Doctors take the cerebrospinal fluid from patients and check whether it contains the expected mixture of proteins - the expected type 4, but now with an equal or more mixed 2.

By the time people start to forgetnames and where the keys to the car, the changes in the brain have been a dozen years. This means that patients who join the study may not count on much. It will be too late for them.

Despite this, the fund is searching for drugs fromAlzheimer's gave Crystal $ 3 million for research. In the end, there is hope that middle-aged people with genes at risk will be able to undergo a single genetic tune. Even a small decrease in the rate at which changes in the brain occur can change the situation over time.

Well, let's hope everything works out. We offer to follow the news on our news channel.