Protection of neuroprotectors!

Cooperation of the Institute of Molecular Genetics of the Russian Academy of Sciences, Lomonosov Moscow State University and the Innovative Research and Production Center "Peptogen" on the development, clinical trials and release of "Semax", a drug for stimulating brain functions in extreme conditions, is one of the few examples of successful public-private partnership in the field of innovative medicines. About the discovery of new properties of the drug and the latest research on the development of other peptide drugs – Nikolay Fedorovich Myasoedov, Deputy Director for Research, Head of the Department of Chemistry of Physiologically Active Substances of the Institute of Molecular Genetics of the Russian Academy of Sciences, Doctor of Chemical Sciences, Academician of the Russian Academy of Sciences (left) and Andrey Aleksandrovich Kamensky, Head of the Department of Human and Animal Physiology of the Faculty of Biology of the Moscow State University. M.V. Lomonosova, Doctor of Biological Sciences, Professor (right).

Semax was the first peptide-based drug created as part of a partnership between your organizations. Are you still working on peptides?– Nikolay Myasoedov (N. M.): Yes, we continue.

Our latest research in the field of peptides is related to the development of painkillers. We study, in particular, a peptide isolated in 1983 from the skin of a South American frog called dermorphin, one of the fragments of which has analgesic properties. We are conducting these studies together with the V.V. Zakusov State Research Institute of Pharmacology of the Russian Academy of Medical Sciences. Moreover, we are the first in this area, there are no peptide analgesics as such yet.

Another area of research is the search for peptide drugs with antiviral properties. We are carrying out these works under a state contract with Rosnauka and also in partnership, this time with the N.F. Gamalei State Research Institute of Epidemiology and Microbiology of the Russian Academy of Medical Sciences and CJSC Innovative Research and Production Center "Peptogen". I hope that in 2009 we will make significant progress in this direction. In any case, we will develop some optimal structure that has antiviral properties.

We are also working on the creation of amino acid sequences with neuroleptic properties. There are a number of drugs called antipsychotics (or neuroleptics) such as clozapine. Compared with conventional molecules, peptide neuroleptics have significant advantages, because they decompose in the body as soon as they do their job. We are conducting these studies together with specialists from the Scientific Center of Mental Health of the Russian Academy of Medical Sciences.

We have also created a peptide drug that helps with peptic ulcer and diabetes (especially, as we believe, it will be useful for type 2 diabetes), and at the same time has antithrombic properties (roughly speaking, it dilutes the blood, making it less thick, which is very important for the elderly). Its working name is "IAP–1". He is still at the stage of preparation for preclinical studies.

Many years of work on the study of a new group of peptides, which we called glyprolins, is nearing completion.

Help STRF.ru:
Peptides are physiologically active organic substances that act as intermediaries between cells. By binding to the receptors of the cell, they transmit certain signals to it, maintain the normal activity of the central nervous system, for example, help the work of brain neurons, regulate emotions. Peptides have "antagonists" – special proteins that break them down to amino acids. In the human body, peptides live from a few seconds to tens of minutes, managing to fulfill their mission during this period. Often it is the balance between the formation of peptides and their breakdown in our body that determines the norm and pathology. On the basis of peptides, scientists create neuroprotective drugs that successfully combat the most severe disorders of the nervous system – neurasthenia, stroke, leading to the death of brain neurons and, as a consequence, paralysis and paresis. Such drugs have minimal side effects, because the peptides themselves have a great similarity with certain proteins present in the human brain. The research of Semax on animals continues at the department under your leadership.

What for? After all, the drug is already allowed...– Andrey Kamensky (A. K.): We continue to study the drug "Semax" in rats in order to expand the range of its therapeutic use and increase the duration of the effect of action.

We are trying to create more effective analogues of it. Also, maybe we will develop an "antagonist", that is, a drug with the opposite effect. When various Semax analogues were tested, those that, unlike him, on the contrary, worsened memory were found. But after all, a drug that can "turn off" memories for a while may also be in demand.

Semax also had such an interesting effect. When it was administered to elderly people suffering from memory disorders, their memory was not restored as much as senile depression was removed. Patients noted an improvement in their well-being, asked to inject the drug again. This is already an emotional sphere, where completely different mediators are involved, and it is also interesting for us to conduct research and understand all this. We are also interested in checking how the therapeutic effect of Semax manifests itself in new models of Parkinson's disease and Alzheimer's disease.

All this implies a large amount of research. Yes, the drug is allowed and has almost no side effects (because, in fact, it is an element of the protein of cells of the central nervous system), but it is quite difficult to predict any additional properties without animal testing. When a peptide drug binds to a cellular receptor, the signal from this receptor must be transmitted inside the cell. Then she will change her job. For example, he will not die from a decrease in oxygen supply. But very often the drug binds to the receptor, and the signal does not go to the cell. And it only gets worse: even a person's own peptide can no longer act, since the receptor is bound by a medicinal substance – a synthetic peptide.

An equally important issue that we are studying is the duration of the therapeutic effect of peptide drugs. To all peptides, without exception, that I know of, a person quickly develops tolerance. It is also interesting to work with this, to ensure that this does not happen. We are trying to somehow modify the Semax molecule so that the body stops "recognizing" it, and the therapeutic effect of the drug would be preserved. To solve this problem, we mainly use the method of computer modeling, which, of course, greatly facilitates, but in no way replaces animal testing.

How would you assess the level of domestic developments for the pharmaceutical industry, in particular, research in the field of peptides?– N. M.: I think the research of peptides in Russia corresponds to the world level.

Serious work in this direction is carried out at the Institute of Bioorganic Chemistry. Academicians M.M. Shemyakin and Yu.A. Ovchinnikov of the Russian Academy of Sciences, V.V. Zakusov Institute of Pharmacology of the Russian Academy of Medical Sciences, in the Russian Cardiological Research and Production Complex of Rosmedtechnologies. And this is not just research on peptides, it is research close to the creation of drugs. According to various estimates, out of 30-50 different peptide preparations that were registered in the world by 2005, 10-15 were Russian. Currently, 60-90 more peptide preparations are at different stages of research. Five of them are Russian, God forbid. So the years of lack of money, brain drain still had a strong effect.

Is IMG RAS planning to issue international patents for Semax and Selank drugs?– N. M.: A difficult question.

Large Western pharmaceutical companies, as a rule, always keep the formula of the active substance of the drug in the mode of know-how, trade secrets. When the drug is already put into production, it is patented, but in such a way that it is not possible to "repeat" its production in a territory that the patent does not cover.

The institute, in order to formalize property rights to new medicines, must patent its developments.

We received a domestic patent for Semax back in the days of the USSR, the formula of the drug has already been published and has become world property. This patent protects our rights only on the territory of Russia and the CIS. And in France, Germany, England, the USA, its formula can be freely used, and our patent law does not prevent this.

We tried to do something different with Selank. There is a PCT procedure (Patent Cooperation Treaty with English – "patent cooperation agreement" – ed.), according to which a patent application is considered filed simultaneously in Russia and other countries and is valid from 28 to 32 months. During this time, you need to issue a patent in the country in which you want to secure the rights to a new drug: in England, in Japan, in America. The Academy of Sciences has allocated sufficient funding for this. And that's tens of thousands of dollars.

Your second drug, Selank, as far as I know, has been slowing down with registration for the third year. Why?– N. M.: Registration of Russian drugs in general is extremely difficult.

I would love to know which department is responsible for the introduction of new domestic drugs. Something tells me that none of the officials are interested in this.

– A. K.: I see how Nikolai Fedorovich and his employees have been knocking out some pieces of paper for years… It is incredibly difficult, almost impossible, to get through all these administrative obstacles. If academician of the Russian Academy of Medical Sciences, director of the V.V. Zakusov Institute of Pharmacology of the Russian Academy of Medical Sciences Sergey Seredenin, one of the co-authors of Selank and one of the first people in the pharmacological world and in the Pharmaceutical Committee, cannot "push" a native drug…

As a rule, the whole problem is in the paperwork. After sending the drug for registration, you wait for a month, two, then you get the answer that two commas are not in place, they require rework. And if the developer of a new drug is from Novosibirsk? As long as he waits for his drug to be "carried out" in Moscow, then either the drug will no longer be needed, or he himself will simply not live. That's scary.

Abroad, the registration process of drugs is strictly formalized. There we are talking sometimes about two or three days: which of the firms will have time to register earlier? Companies compete fiercely, develop drugs in parallel, even know-how theft occurs… We don't have this yet: even if they steal it, they won't register it anyway. At least some plus.

How is the cooperation between IMG RAS and CJSC Peptogen built?– N. M.: Peptogen CJSC is our institute education, a kind of continuation of IMG RAS in the innovation sphere.

The company rents premises from the institute, on part of which it produces Semax, on part it has organized production facilities for the production of another drug – the drug Selank, which helps to get rid of pathologies of the nervous system, in particular, feelings of anxiety, depression, etc.

We have concluded licensing agreements with Peptogen, under which we receive five percent royalties from the volume of sales of manufactured products and invest this money in exploratory research and development of new drugs. (By the way, usually in pharmaceuticals royalties do not exceed two to four percent.)

Our partner also picks up new developments after preclinical trials, for example, the same drug "IAP-1", and invests money in preclinical and clinical studies.

And what does a private company get in return?– N. M.: Our personal guarantees to provide a license.

The institute cannot transfer intellectual property rights. I would call it a partnership based on trust.Do you receive orders from Peptogen CJSC for the development of new drugs?

– N. M.: It is impossible to order a scientific idea, including the idea of a new drug.

It is born in the head of a scientist. It can be reached only as a result of problem-searching research.

For example, such a huge pharmaceutical company as Novartis, whose turnover is about $ 60 billion, allocates three to five billion dollars a year to science. And these, as it is believed, "lost money" is initially put into the costs of creating any medicine, which on average amount to about $ 500 million. We don't have such powerful pharmaceutical companies that can invest comparable money in research without expecting high returns. Therefore, it is almost impossible to develop new drugs in Russia without the support of the state.

And how clearly can the medical community formulate such an order, for example?– N. M.: You see, modern pharmacology is based on the results of three sciences: chemistry gives you structure, physiology – functions, biology – mechanism of action.

To order a drug, you need to be an expert in all these sciences, plus be aware of the so–called "social order" - what society needs.

Mikhail is Found talking, STRF.ruPortal "Eternal youth" www.vechnayamolodost.ru

23.03.2009