How a drug for Alzheimer's disease is being developed in Russia

Vladimir Koryagin, "Newspaper.Ru" 

How a drug for Alzheimer's disease is being developed in Russia, what are the dangers of incurable neurodegenerative diseases and why the future belongs to multipurpose drugs, the science department of Gazeta found out.Ru».

Neurodegenerative diseases can rightly be called the scourge of the XXI century. Many of them were identified and described only at the beginning of the last century or at the end of the XIX century. Over the past hundred years, researchers have not yet found an effective way to combat them. At the same time, for example, almost 27 million people suffer from Alzheimer's disease in the world. This number is growing every year, including due to the increased average life expectancy. Effective ways to resist such ailments are also being sought in Russia.

According to experts, there are about 1.5 million people in our country suffering from dementia, including Alzheimer's disease. "These 1.5 million patients are an impressive figure. It is known that with diseases such as Alzheimer's, Parkinson's and amyotrophic lateral sclerosis, a complete cure of the patient is currently impossible," he told the newspaper.Ru" Doctor of Chemical Sciences, Corresponding Member of the Russian Academy of Sciences, Director of the Institute of Physiologically Active Substances of the Russian Academy of Sciences Sergey Bachurin, together with colleagues engaged in the development of a drug to combat Alzheimer's disease.

According to him, the existing drugs are symptomatic, that is, they improve the condition for a while, but do not slow down the development of diseases. Thus, the disease continues to progress even against the background of the use of these drugs.

This is largely due to the fact that such diseases have a multifactorial nature, that is, they are caused by a whole group of interconnected biological objects located in the central nervous system. It should also be noted that all existing drugs are foreign developments.

"Therefore, the search for drugs that act on one target – and this is how the traditional scheme of creating medicines is built – in this case cannot be limited. Too many violations occur in parallel, it is necessary to find a comprehensive approach," says Sergey Bachurin.

One of the promising approaches to solving this problem is to create multiligand compounds capable of simultaneously acting on several targets that are involved in the pathogenesis of the disease. Such a multi-targeted drug will affect a number of fundamentally important stages in the development of the disease.

The essence of the project "Directed design, synthesis and research of the biological activity of multitargeted compounds as innovative drugs for the treatment of neurodegenerative diseases", implemented with a grant from the Russian Science Foundation, is to create such multitargeted drugs to combat Alzheimer's disease.

An article was published in the journal Scientific Reports, part of the Nature Publishing Group, in which researchers presented for the first time the results obtained during the research (Makhaeva et al., Conjugates of γ-Carbolines and Phenothiazine as new selective inhibitors of butyrylcholinesterase and blockers of NMDA receptors for Alzheimer's Disease, in open access – VM).

"We can say that we have announced the creation of a new original group of multi-targeted drugs. It is shown for the first time that it is possible to change the enzyme profile of the compound in a directed manner. We managed to obtain substances that simultaneously act on cholinesterase enzymes and some types of glutamate receptors," Sergey Bachurin shared.

In general, Russian researchers are trying to solve fundamental scientific and practical problems at the same time. On the one hand, we are talking about the search for new biological targets, which are fundamental from the point of view of therapeutic use. And this, in turn, will allow us to understand how the disease develops, because the mechanisms of the pathogenesis of Alzheimer's disease are still unclear. On the other hand, the results obtained should be the basis for the creation of original domestic medicines.

"The path from a biologically active compound to a drug is very long and thorny. Not everything that is good in the laboratory works effectively on humans," says Sergey Bachurin.

Currently , in the world , work in the field of creating drugs for the treatment of neurodegenerative diseases is carried out mainly in the following areas: the search for neuroprotective substances acting on the pathogenesis of the disease and capable of blocking the development of the disease, in particular effective multi-targeted drugs, the search for new targets involved in the development of the disease, and finally, repositioning of known drugs for a new application is very attractive from the point of view of business.

Similar programs exist, for example, in the USA and Europe. They allow the use of well-known drugs for completely new purposes, including the treatment of neurodegenerative diseases.

As part of this strategy, the domestic antihistamine drug "Dimebon" was previously tested for the treatment of Alzheimer's disease, which showed good results in the second phase of clinical trials.

The success of such research also depends on contacts in the business environment. Sergey Bachurin's group actively cooperates with pharmacological companies that help to conduct clinical trials. In addition, contacts have been established and are developing well with the universities of Cardiff (Wales), Maastricht (Netherlands), Würzburg (Germany) and Lisbon (Portugal).

According to Sergey Bachurin, sanctions and the complicated political situation have, fortunately, not greatly affected cooperation with business partners and foreign scientific institutes and universities.

The main problem for the development of research is now associated with a sharp decline in the ruble exchange rate, which has led to a significant increase in the cost of scientific equipment and reagents, which are mainly produced abroad.

At the same time, the economic damage from Alzheimer's disease and other neurodegenerative diseases is much higher. In 2010, it was about $600 billion, and now it has exceeded this value. The work of Russian researchers, in addition to the huge social significance associated with improving the quality and life expectancy of people in old age, should serve as an impetus to the development of domestic pharmaceuticals. After all, the creation of even one relevant innovative drug on the basis of scientifically based approaches can give an economic effect of several hundred million rubles a year.

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01.10.2015