Alzheimer's disease in silico
Scientists from Russia have calculated the optimal way to treat Alzheimer's disease
Biomathematics from the Institute of Systems Biology in Moscow and their foreign colleagues have developed an optimal strategy for combating Alzheimer's disease by calculating the ideal start time and minimum treatment time, and published it in the journal CPT: Pharmacometrics & Systems Pharmacology.
"We do not make loud statements that we have understood the cause of Alzheimer's disease. We have shown that our model helps to evaluate hypotheses quickly and efficiently. The most important question we wanted to answer is: how to help the patient? We were able to determine the optimal treatment regimen, but whether it will really improve the patient's life is not yet clear. This requires real clinical trials," says Tatiana Karelina from Institute of Systems Biology in Moscow.
A tangled tangle of memories
Both Alzheimer's disease and Parkinson's disease are caused by the accumulation of various protein "garbage" in nerve cells, which gradually kills neurons in different parts of the brain. Their death leads to memory loss and senile dementia in the first case and to loss of control over the limbs in the second.
Scientists do not yet understand the mechanisms that cause brain cells to accumulate tau protein, beta-amyloid plaques, alpha-synuclein tangles, and other potential causes of these diseases. Therefore, biologists not only cannot create drugs for Alzheimer's and Parkinson's diseases, but also understand why they develop.
Russian scientists propose to solve this problem mathematically, without resorting to lengthy and expensive experiments. Mathematicians from the Institute of Systems Biology recently took the first step in this direction by creating a computer model of how beta-amyloid plaques are formed.
It can significantly speed up the search for a cure for Alzheimer's disease, since such calculations make it possible to predict the effectiveness of various substances on protein accumulations without conducting real experiments in the laboratory.
This model has already helped scientists uncover the reasons why some promising drugs for Alzheimer's disease failed in clinical trials, but it did not describe exactly how the disease develops.
Health Formula
Russian scientists and their foreign colleagues solved this problem – they analyzed the results of several dozen clinical studies on how amyloid plaques grow in the brains of humans and animals, and "translated" their conclusions into the language of mathematics understandable for a computer.
The fruit of all these efforts was a set of formulas with 30 variables, with the help of which Karelina and her colleagues were able to identify several key factors in the development of the disease and understand how and for how long it should be treated.
In particular, it turned out that the main reason for the development of Alzheimer's disease is that brain cells lose the ability to decompose insoluble accumulations of beta-amyloid on their own, which leads to the formation of plaques and mass death of neurons.
Further calculations showed that all existing and future drugs that destroy beta-amyloid plaques can have a serious effect on the patient's brain only if treatment is started as early as possible, no later than 60 years, and it should last at least a year.
Now Russian mathematicians are preparing their model for presentation at the American Conference on Pharmacometrics – the most important annual event for developers of new drugs. Scientists hope not only to discuss their results with the community, but also to find new partners for further work.
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29.09.2017