Diabetes medicine will help parkinsonics

Restoring energy metabolism can help in the treatment of Parkinson's disease

Anna Stavina, XX2 century

The drug, originally developed for the treatment of type 2 diabetes, is being prepared for trials as the first tool that can slow the progress of Parkinson's disease. The corresponding study was published in the journal Science Translational Medicine (Ghosh et al., Mitochondrial pyruvate carrier regulates autophagy, inflammation, and neurodegeneration in experimental models of Parkinson's disease).

"We hope that soon a turning point will come in the lives of millions of people living with Parkinson's disease," says lead author of the study, Dr. Patrick Brundin, director of the Center for Neurodegenerative Diseases (Center for Neurodegenerative Science) of the Van Andel Research Institute (VARI) and head of the Committee on conducting clinical trials of The Parkinson's Disease Treatment Foundation (The Cure Parkinson's Trust's Linked Clinical Trials Committee). "All the tests conducted on model animals indicate that this drug, in principle, can slow down the progress of Parkinson's disease in humans as well."

Until now, the treatment of Parkinson's disease has involved fighting the symptoms of the disease. If MSDC-0160 successfully passes clinical trials in humans, it may become the world's first drug that affects the disease itself and slows down its course. Thus, the drug will improve the quality of life of patients, preventing falls caused by the disease and deterioration of cognitive functions. It can also reduce the need for existing medications or delay their appointment, which, according to Dr. Brundin, is important because these drugs cause serious side effects.

Parkinson's disease affects 7-10 million people worldwide, and as life expectancy increases, the number of patients with this disease is expected to grow rapidly. Currently, there is no effective cure for Parkinson's disease, and the list of first-line drugs prescribed to patients has not changed significantly since the 1960s, when levodopa appeared in clinical practice.

Tom Isaacs, co-founder of the Parkinson's Disease Treatment Foundation, has been suffering from this disease for 22 years. He claims that MSDC-0160 is one of the most promising drugs from those that were considered by the international council of experts of the Foundation.

"Our scientific department has evaluated more than 120 drugs that theoretically can affect Parkinson's disease. MSDC-0160 really has the necessary qualities to become a breakthrough in the treatment of this disease, seriously and permanently affecting the lives of patients in the near future, – says Aizaks. – We are working to start human trials of the drug as soon as possible."

MSDC-0160 was developed by the medical startup Metabolic Solutions Development Company for the treatment of type 2 diabetes. In 2012, Dr. Brundin decided that the drug has good potential as a candidate drug for the treatment of Parkinson's disease due to its principle of action, proven safety when used in humans, accessibility and interest of the company's employees in projects to change the prescription of drugs. At the end of 4 years of work, the results that MSDC-0160 demonstrated in the laboratory exceeded Dr. Brundin's expectations.

The unusual principle of action of the drug MSDC-0160 is based on the recent discovery of the causes of Parkinson's disease. It turns out that it is caused, at least in part, by a metabolic disorder. MSDC-0160 regulates the work of mitochondria in brain cells, restoring their ability to convert nutrients into energy. As a result, brain cells begin to better tolerate interaction with potentially harmful proteins, which reduces the activity of the inflammatory process and reduces the number of dying brain cells.

"Parkinson's disease and diabetes mellitus can manifest themselves in completely different ways and lead to different outcomes. However, we found that at the molecular level, these diseases are characterized by common mechanisms, and the response to treatment with a new class of drugs that increase insulin sensitivity, for example, MSDC-0160, may be similar," says Jerry Colca, co–founder, president and scientific director of the startup Metabolic Solutions Development Company.

Although Dr. Brundin is focused on launching clinical trials of MSDC-0160 in patients with Parkinson's disease, he is also optimistic about the possibility of investigating the effectiveness of a new drug for the treatment of dementia with Lewy bodies and other diseases characterized by cognitive impairment, such as Alzheimer's disease.

"This is a very promising area of research," Dr. Brundin notes. "Regardless of what results we get during the upcoming clinical trials of MSDC–0160 as a treatment for Parkinson's disease, we now have a path that can be followed in the search for drugs that can cope with the causes of this and many other insidious diseases."

Levodopa (L-dopa, 3,4-dihydrophenylalanine) – a chemical precursor of dopamine, a neurotransmitter, the level of which decreases in patients with Parkinson's disease. A mixture of L- and D-isomers of this substance was first synthesized by the Polish biochemist Casimir Funk in 1911 and two years later isolated by the Swiss pharmacologist Markus Guggenheim from the fruits of the leguminous plant Vicia faba (garden bean). However, taking the mixture caused severe nausea and vomiting. A pure levorotatory isomer was synthesized in 1921, but at that time no one was interested in the discovery and was not even patented.
The period of active study of levodopa occurred in 1950-1960 . XX century. Attempts to use the drug in clinical practice were fraught with a number of failures, until the American neurologist and neuropharmacologist George Cotzias suggested using large doses of the drug: from 3 to 16 g per day.
Despite serious side effects (in particular, nausea, vomiting and uncontrolled movements), levodopa remains one of the main antiparkinsonian drugs currently used.

Portal "Eternal youth" http://vechnayamolodost.ru  12.12.2016