Smooth fruit: strawberry substance will restore movement in Parkinson's disease

Russian scientists have created a chemical compound that will help patients with Parkinson's disease regain the ability to move. The developers were able to confirm these properties of the new molecule in experiments on worms and fish, which, after exposure to the neurotoxin and subsequent treatment, moved as actively as healthy individuals. According to doctors, their options in neurodegeneration therapy are currently limited by alleviating symptoms, so doctors need new effective drugs. However, work on a promising product has just begun, and it may take a long time to enter the market.

Restoration of motor functions

Scientists from Lomonosov Moscow State University and the Moscow Institute of Physics and Technology have synthesized and tested a compound capable of effectively restoring motor activity in Parkinson's disease. The results of the study are published in the journal Bioorganic Chemistry. The means currently available to doctors to combat this pathology can only slow down its development, so doctors are extremely interested in finding new effective drugs that can be created based on a new molecule.

— We were able to show that the new compound ORA471 is not only low-toxic, but also effectively restores motor function in a nematode model of Parkinson's disease. The worms that received the toxin moved much slower and had less control over their movements. However, when OR471 was added, their motor parameters — distance traveled and speed — returned to the values of the healthy control group. This indicates the great potential of the molecule for further development of therapy for neurodegenerative diseases," said Elena Marusich, co—author of the work, senior researcher at the Laboratory of Personalized Chemoradiotherapy at MIPT.

The scientists used the synthetic compound serratin (AN2) as the basis for the substance, an analog of the natural substance urolitin A, which is found in pomegranates and strawberries and is already known for its ability to trigger autophagy, that is, the process of removing chemical toxic debris that kills neurons. On its basis, the researchers synthesized a library of 27 new molecules.

The OR471 molecule became the leader among the synthesized compounds. During experiments on human neuroblastoma (malignant nerve cell) cell lines, it showed significantly higher activity in triggering autophagy and eliminating damaged mitochondria compared to the original serratin, as well as lower toxicity. Scientists have found that ORA471 affects the mitochondria, the energy stations of the cell, gently affecting the processes of oxidation and energy production.

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Implementation of the development

The safety of the new compound was confirmed by tests on three biological models: C. elegans nematodes (roundworms), zebrafish embryos and mice. The maximum tolerated dose for mice was 300 mg/kg of body weight. This makes it possible to classify ORA471 as a moderately dangerous substance and confirms its prospects for further research. Another experiment was performed on zebrafish, in which parkinsonism was modeled using neurotoxins.

— The main interest of our work is that the compound does not act like classic symptomatic drugs, but affects one of the fundamental cellular mechanisms — autophagy. We have shown that our molecule is capable of activating autophagy and mitophagy, which is the removal of damaged mitochondria. In the fish model, this was accompanied by an improvement in motor activity," said Alexander Rudenko, the first author of the study, a junior researcher at the Belozersky Research Institute of Physico—Chemical Biology.

However, there is still a long way to go before creating a full-fledged medicine. So far, this is only a promising mechanism of action that can potentially form the basis of new approaches to the treatment of neurodegenerative diseases. For further development, it is necessary to optimize the structure of compounds, test their safety and efficacy on more complex models, study pharmacokinetics, dosages, possible side effects, and then conduct preclinical and clinical studies. This path usually takes years, and often more than ten years, the specialist emphasized.

— We need new tools that could alleviate the condition of patients with Parkinson's disease. New medicines appear very rarely, and we usually use something that has been around for quite a long time. Research is underway in this direction, but they have not yet reached the point where a specific drug appears on the market. I think this is due to the fact that it has not yet been possible to prove their effectiveness," said Maria Medvedeva, chief physician of the boarding house of the Russian Academy of Sciences.

According to her, existing medicines cannot stop the development of pathology, but can only alleviate symptoms in order to reduce the patient's disability. At the same time, the disease always proceeds individually, so it is important to prescribe a suitable combination of drugs for a particular person. Otherwise, the side effects can be very severe.