Scientists from Russia found out why not working a cure for the disease of Alzheimer

© Fotolia / ktsdesignСтроение neuron of the brainScientists from Russia found out why not working a cure for the disease of Alzheimer© Fotolia / ktsdesign

Scientists from the Institute for systems biology have developed a mathematical model that allows to evaluate the effectiveness of potential medications for Alzheimer’s disease, without conducting experiments on human volunteers or animals, according to an article published in the journal CPT Pharmacometrics & Systems Pharmacology.

«We created a structural model, calibrated on a large dataset. It is very easy to compare the results of analyses of cerebrospinal fluid with real processes in the brain of the patient. In fact, we can now assess will work a drug or not in advance, knowing its parameters. This will greatly accelerate the development of therapies and improve the accuracy of selection,» – says Tatiana Karelina from the Institute for systems biology in Moscow, quoted by the press service of the organization.

It is believed that Alzheimer’s is caused by the accumulation in neurons of pathogenic substances, the protein beta-amyloid. It is formed from «scraps» of the APP protein, which is involved in the processes of repair of the damaged neurons and in the formation of connections between them. Violations in recycling of molecules of this protein leads to the appearance of plaques of beta-amyloid and the destruction of nerve cells.

In recent years, scientists have created dozens of prototypes of drugs for Alzheimer’s disease, purifying cells from beta-amyloid or preventing their formation. All of these drugs or did not reach clinical trials because of powerful side effects, or failed in them, which has led many researchers to believe that Alzheimer’s disease may not be associated with protein APP and its «recovery.»

Tatyana Karelina and her colleagues at the Institute, as well as experts of the company Pfizer decided to approach this problem from the other side, creating a computer model of plaque formation of beta-amyloid and development of Alzheimer’s disease, which can predict how will behave a particular drug in the patient’s body at different stages of disease development.

This model, as the scientists tell, incorporate differences in the brain of primates, mice, and humans, which is extremely important for understanding how to relate the results of experiments on animals and the possible influence of different prototypes of drugs for Alzheimer’s disease on human brain cells.

As shown by calculations of the Russian scientists, previous failures in clinical trials can be related to the fact that their authors are «directly» transferred the results of experiments on mice, per person adjusted for differences in mass and speed metabolism. It turned out, was absolutely incorrect approach.

Mathematical equations deduced by scientists have shown that in rodents and higher primates not only is the rate of production of beta-amyloid and activity of certain genes associated with Alzheimer’s disease, but the barrier between the brain and the circulatory system is designed them quite differently. On the other hand, a significant difference between man and APE Karelina and her colleagues found that allows you to use the results of the experiments on primates to develop a cure.

As the researchers note, their model even predicted that the optimal regimen of medicines of new generation will be to maximize the fragmentation of the doses of the substance during the day. According to scientists, their achievements are already interested in the pharmaceutical industry and they are negotiating with them for their implementation in the process of drug development for Alzheimer’s disease.

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