Kurchatov Institute: A drug for the treatment of Parkinson's disease in the early stages

Main article: Parkinson's disease

2024: Introducing a drug to treat Parkinson's disease

Scientists of the St. Petersburg Institute of Nuclear Physics named after B.P. Konstantinov (PINF) Research Center "Kurchatov Institute" together with colleagues from the First St. Petersburg State Medical University named after I.P. Pavlov patented a drug for the treatment of Parkinson's disease in the early stages. It acts on the enzyme glucocerebrosidase, which is encoded by the GBA1 gene. Mutations in this gene increase the risk of developing pathology tenfold. The Kurchatov Institute announced this on March 22, 2024.

source = Kurchatov Institute

With a decrease in glucocerebrosidase activity, a substrate accumulates in cells. It can stabilize neurotoxic forms of the alpha-synuclein protein that cause neurodegeneration. The molecule we developed collects the enzyme in such a way that it works more efficiently, - said Sofya Pchelina, head of the laboratory of human molecular genetics at the Kurchatov Institute - PINF.

When developing the drug, Russian scientists took as a basis the research of foreign colleagues who managed to correct the work of the enzyme with the help of a small molecule - pharmacological chaperone (this molecule can restore the structure of protein formations).

A computer model of glucocerebrosidase was built at the Kurchatov Institute Research Center - PINF and began to look for chemical modifications of chaperone that could increase the effectiveness of its action. The scientists then synthesized several molecules and tested how they affected the enzyme's activity in cells of patients with a mutation in the GBA1 gene. For the experiment, the researchers chose macrophages (cells that capture and digest bacteria) where glucocerebrosidase shows maximum activity.

Experiments have shown that the resulting compound more effectively reduces the amount of harmful substrate causing neuronal degradation than foreign drugs (which are already undergoing clinical trials abroad).

According to scientists, the tool they created has a preventive effect: it can prevent the death of neurons. Therefore, the medicine must be used at the earliest stages of the development of the disease.

First of all, the drug is designed for carriers of mutations in the GBA1 gene - this is a high-risk group, about 5-10% of all patients with parkinsonism. However, some studies show that glucocerebrosidase activity is reduced in all forms of Parkinson's disease. If this is confirmed, the medicine will suit everyone who has faced a diagnosis. In addition, the drug may be useful in Gaucher disease (a rare and severe disease also associated with glucocerebrosidase deficiency).