MOSCOW, June 15 Scientists from the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences (ICiG SB RAS) are conducting research on the treatment of neurodegenerative diseases with drugs that are now used to treat other diseases. According to them, the study of molecular processes in healthy neurons and cells with pathologies will help in adapting registered medicines to expand their scope.
New biologically active substances are constantly extracted from natural materials and synthesized from scratch, according to the institute. But the process of introducing them as medicines is much slower.
The scientists explained that in order to enter the market, the drug must pass at least four phases of clinical trials. Depending on the disease, this process can take several years, or it can take decades. This forces specialists to work to expand the scope of drugs that have passed all clinical trials, as some of them can treat several diseases at once.
During the research in this area, specialists from the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences collected a large library of stem cells from patients with neurodegenerative diseases: Parkinson's, Huntington's or Alzheimer's disease; atherosclerosis, amyotrophic lateral sclerosis and others. These cultures are induced pluripotent stem cells (iPSCs).
To create iPSCs, body cells are «reprogrammed» so that they acquire the characteristics of embryonic stem cells. These are undifferentiated cells, upon exposure to which it is possible to obtain mature cells of an adult with a certain function. They can be stored in a deep freeze for a long time, and if necessary, thawed and cultivated in the required volumes.
“Any types of cells of the human body can be obtained from iPSCs and assess, for example, cardiotoxicity, hepatotoxicity of compounds, therefore, such cell models are a very convenient“ tool ”for studying the effect of drugs,” said Anastasia Malakhova, senior researcher at the Laboratory of Developmental Epigenetics of the Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences .
Specifically for this study, stem cells from patients with Parkinson's disease and Huntington's chorea will be used. They will be transformed into neurons and exposed to active ingredients from existing drugs for other diseases, the scientists explained.
«We can add the drug in various concentrations to the nutrient medium for neurons and observe changes in molecular processes in the cell. Whether the drug increases the viability of neurons, whether its addition leads to a decrease in oxidative stress,» Malakhova specified.
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She added that in the joint work of scientists from the Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences and the Institute of Chemical Biology and Fundamental Medicine of the Siberian Branch of the Russian Academy of Sciences, drugs will be used that prevent the action of the enzyme poly(ADP-ribose)-polymerase-1 in cells, which, in addition to numerous other functions, is involved in one of pathways of cell death — parthanatose.
Today, poly(ADP-ribose)-polymerase-1 inhibitor molecules are used to treat cancer, but according to many evidences, they also have a neuroprotective function, the expert emphasized.
«In our work, we use the most advanced methods of cell biology: reprogramming a somatic cell into iPSCs and editing the genome using CRISPR/Cas9 technology, which allows us to introduce biosensor transgenes into cells to track changes in a living system,» said Malakhova.
She explained that biosensors make it possible to observe in real time the processes leading to the death of neurons in neurodegenerative diseases (which include Parkinson's, Alzheimer's, Huntington's chorea and many others).
The team of authors plans to present the first results of the study at the CRISPR-2023 congress, which will be held in Novosibirsk Akademgorodok in September 2023.
The study was supported by the Russian Science Foundation (grant no. 23-15- 00224).