Stop Parkinsonism
Researchers from Johns Hopkins University have developed an experimental drug similar in structure to antidiabetic drugs that slows down the progression of Parkinson's disease. In experiments conducted on human brain cell cultures, as well as on mouse models, the drug stopped damage to neurons.
It is expected that clinical trials of the drug NLY01 will begin this year. The authors explain that if the planned studies are successful in humans, NLY01 may become one of the first drugs for the treatment of Parkinson's disease aimed directly against damage to neurons, and not just symptoms (muscle rigidity, cramps, fatigue, dizziness, and others).
NLY01 belongs to the group of glucagon-like peptide-1 (GLP1R) receptor agonists. This mechanism is widely used in the treatment of type 2 diabetes mellitus. In previous animal studies, the neuroprotective potential of GLP1R agonists has been noted, but how it works in the brain has not been studied.
To clarify this, the researchers tested NLY01 on three main types of human brain cells: astrocytes, microglia, and neurons. They found that microglia (immune brain cells) had the largest number of receptors binding to NLY01 – twice as many as other cell types, and 10 times more in Parkinson's disease compared to healthy people.
It is known that microglia secrete chemical signals that transform astrocytes that help neurons interact with each other into "activated" aggressive forms (A1) that destroy connections between brain cells and cause neuronal death.
The researchers suggested that NLY01 inhibits this transformation and thereby slows down the progression of Parkinson's disease. They treated NLY01 microglial cells and found that the activating signals had disappeared. The healthy astrocytes introduced into the culture did not turn into A1 and remained healthy.
Next, the researchers tested the effectiveness of the drug on mouse models of Parkinson's disease. The animals were injected with alpha-synuclein, a protein that triggers the disease. NLY01 injections were given to an experimental group of mice, the control group did not receive any treatment. After 6 months, all mice passed behavioral tests. The lack of treatment led to the development of motor disorders characteristic of Parkinson's disease. Mice treated with NLY01 retained normal motor functions.
In another experiment, mice were used in which, after gene modification, the synthesis of human alpha-synuclein was increased – thus a model of the hereditary form of Parkinson's disease was created. Under normal conditions, such mice died after 387 days. However, 20 mice treated with NLY01 lived 120 days longer.
Further investigation showed that the brains of mice treated with NLY01 lacked neurodegenerative changes characteristic of Parkinson's disease.
The authors note that the experimental drug should be tested for safety in humans, but based on the safety data of other GLP1R agonists, one should not expect any serious obstacles to use in humans. They hope that NLY01 can improve the lives of patients suffering from Parkinson's disease in a relatively short period of time.
Other GLP1R agonists – exenatide, lixistenatide, liraglutide and dulaglutide – have already been approved for the treatment of type 2 diabetes, the cost of a 90-day course of treatment is about $ 2,000. Unlike analogues, NLY01 has a prolonged effect and penetrates well into the brain tissue.
Article by S. P. Yun et al. Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease published in the journal Nature Medicine.
Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on Johns Hopkins Medicine: Experimental Drug Stops Parkinson's Disease Progression in Mice.