Diabetes drug shows promise as first treatment to slow the progression of Parkinson’s

In laboratory models of the disease, the drug restored critical cell functions.

Parkinson’s disease affects 7-10 million people worldwide. There is no cure, and until now, treatment has focused on managing symptoms. Now researchers believe they have found a way to treat the underlying disease itself and slow its progression. The drug, originally developed for type 2 diabetes, worked well in a host of experimental models. The team are now pursuing a clinical trial, which they hope to begin next year. The study was published today in the journal Science Translational Medicine. We spoke with lead author Patrik Brundin of the Van Andel Research Institute to find out more.

ResearchGate: What is MSDC-0160 and how is it typically used?

Patrik Brundin: MSDC-0160 is a promising new investigational drug that was originally developed to treat type-2 diabetes. It improves cellular metabolism, disruptions in which have been implicated not only in diabetes but also in Parkinson’s and Alzheimer’s diseases. When critical metabolic processes run smoothly, brain cells usually clear toxic proteins that accumulate over time. In Parkinson’s disease, problems with cell metabolism prevent these proteins from being removed, which left unchecked, can cause the disease’s symptoms. MSDC-0160 boosts cellular metabolism, ensuring that cellular housekeeping systems clear out these toxic proteins, thus protecting the brain. As an experimental compound, MSDC-0160 has not yet been approved for use in the clinic, outside of trials.

RG: Where did the idea to investigate its effects on Parkinson’s come from?

Brundin: Soon after I moved to Grand Rapids from Sweden in 2012, I had a serendipitous meeting with Dr. Jerry Colca of Metabolic Solutions Development Company in nearby Kalamazoo. We discussed a new class of drugs they were working on that hit a novel molecular target called mitochondrial pyruvate carrier, which seemed to improve cellular metabolism. These compounds had demonstrated effects in laboratory models of Alzheimer’s disease and even had positive effects on sugar metabolism in a small clinical study conducted in patients with Alzheimer’s. Based on these findings and others from the literature, we reasoned that MSDC-0160 may also have an impact in Parkinson’s.

“MSDC-0160 rescued dopamine-producing brain cells in all of our laboratory models.”

RG: How did you assess the drug’s potential as a Parkinson’s treatment in this study?

Brundin: We not only wanted to see whether MSDC-0160 could protect brain cells; we also wanted to understand how it worked. To do this, we used an array of laboratory models, including mice, worms, and cells. For example, we used MSDC-0160 to treat two mouse models of Parkinson’s in three different scenarios. This helped determine the drug’s effects on dopamine-producing cells, which become damaged and die during Parkinson’s. Our cellular and worm models also elucidated MSDC-0160’s effects on dopamine-producing cells. Malfunction of these dopamine-containing cells ultimately leads to the disease’s hallmark symptoms, like tremor and declining motor function. We also kept a careful eye on the drug’s effect on inflammation in the brain, which has long been linked to Parkinson’s. Finally, we used in vitro assays with isolated mitochondria and whole cells, in combination with data from the worm C. elegans, to land on the proposed mechanism of action for MSDC-0160.

RG: What were the results?

Brundin: MSDC-0160 rescued dopamine-producing brain cells in all of our laboratory models. Some of the most remarkable results were in mice, where MSDC-0160 improved behavioral deficits, reduced the loss of dopamine-producing cells and reversed inflammation. Overall, we demonstrated that MSDC-0160 has solid and reproducible positive effects in multiple Parkinson’s models and is a strong candidate for repurposing as a potential treatment.

RG: What are the next steps in this research?

Brundin: We are eager to move this promising therapy into human clinical trials to determine whether MSDC-0160 therapy produces meaningful results for people with Parkinson’s.

“Without getting too far ahead of ourselves, we’re looking at this as a potential first-line treatment for Parkinson’s.”

RG: If human trials are successful, what can Parkinson’s patients expect from this drug?

Brundin: If MSDC-0160 is as successful in the clinic as it has been in the lab, it could slow Parkinson’s disease progression for millions of people, possibly opening the door for many patients to regain some lost function and lessen the need for dopamine-replacement therapies, like levodopa and carbidopa. Positive results could also mean fewer side effects from long-term treatment with current therapies. Combination therapies with MSDC-0160 and dopaminergic drugs may also be an option. It remains to be seen. The first thing we need to do is determine whether this new drug is effective in people. Without getting too far ahead of ourselves, we’re looking at this as a potential first-line treatment for Parkinson’s. The optimal deployment and treatment strategies would be our next set of studies—again, if the human trials are successful.

RG: How common is it for a drug designed to treat one disease to be effective in treating another with such different symptoms?

Brundin: It is not that uncommon for a drug that is being developed for one use to turn out to have other promising applications. Famous examples include Viagra and Rogaine, both of which were originally developed to treat hypertension and ended up as treatments for erectile dysfunction and hair loss, respectively. In our case, the connection between Parkinson’s and diabetes has been well documented. Several studies have shown both diseases originate, at least partially, in cellular metabolism and mitochondrial dysfunction. In fact, this work was supported in part by The Cure Parkinson’s Trust’s Linked Clinical Trials initiative, which is specifically aimed at repurposing drugs to treat Parkinson’s. It’s an extremely promising area.

RG: How does this discovery fit into the broader landscape of Parkinson’s treatments? 

Brundin: We are extremely excited to move MSDC-0160 into rigorously designed clinical trials, which will tell us whether our lab results translate into humans. If so, this could be a game changer. People with Parkinson’s disease often endure not only the devastating effects of cognitive and motor decline, but also the debilitating side effects of current first-line therapies. Successful deployment of this new drug could add decades of health and wellness for millions of Parkinson’s patients around the world.

Additionally, MSDC-0160 is just one prototype in this new class of insulin sensitizers called mTOT modulators. Unlike other drugs that affect a specific enzyme or a cell surface receptor, these molecules work by regulating metabolism. Many more options may soon be available for clinical trials in the treatment of diseases as seemingly diverse as diabetes, Parkinson’s disease, and Alzheimer’s disease. Indeed, another member of this class of drugs, known as MSDC-0602K, is currently in development to treat NASH, a serious form of fatty liver disease.

Featured image: Dopamine-producing brain cells after treatment with MSDC-0160. Courtesy of the Patrik Brundin Laboratory, Van Andel Research Institute.