Can a diabetes drug slow or stop a devastating neurodegenerative disease?

A new clinical trial gives hope to people with multiple system atrophy

Philip Fortier is on a mission: to find a cure for multiple system atrophy (MSA), a devastating neurodegenerative disease that lacks an effective way to halt progression.

For him, it’s deeply personal. His brother, Joe, battled MSA for three years before passing away in 2013. Now, the organization the Fortier family founded — Defeat MSA Alliance — has teamed up with Van Andel Institute and others to support a groundbreaking clinical trial to see if a common diabetes drug called exenatide may also impede MSA’s rapid course.

“There are a great many people around the world suffering from MSA and there are no drugs known to slow it down,” Fortier said. “Right now, there’s nowhere for people with MSA to turn. Anything we can do to help research — to find a drug that can be repurposed to help people — is something we should and must do.”

A tough foe

MSA is a quick and cruel disease. Over the course of five to 10 years, it ravages the body, shutting down the vital systems necessary to keep a person healthy and functioning, such as the ability to move, to regulate heart rate and to digest food.

Although it is considered a rare disease, it affects between 15,000 and 50,000 people in the U.S. Exact statistics are tough to pin down because it is notoriously difficult to diagnose, particularly in its early stages when it often is mistaken for Parkinson’s disease.

Little is known about what causes MSA but, like Parkinson’s, many scientists believe it is linked to a buildup of abnormal proteins called alpha-synuclein, which clog critical cells and cause them to die. In MSA, these cells are the glia, which support and protect the brain’s nerve cells.

The mysteries of its origins are partly responsible for the lack of disease-modifying treatments. Currently, physicians can only treat individual symptoms of MSA, such as sleep problems, dystonia (involuntary muscle contractions) and ataxia (loss of muscle control). Despite similarities between the two diseases, Parkinson’s medications such as levodopa, which replace lost dopamine in the brain, are ineffective in MSA.

“Thanks to a growing body of research, we now know that MSA, Parkinson’s and another related disorder, Lewy body dementia, are all linked by alpha-synuclein,” Fortier said. “That has given us new hope that, with more research, we can possibly find something that gives people with MSA more years with fewer symptoms.”

New hope

The pilot trial is helmed by Prof. Thomas Foltynie in collaboration with colleagues at University College London (UCL) Queen Square Institute of Neurology and the UCLH National Hospital for Neurology & Neurosurgery in London. Two previous small clinical trials by Foltynie’s group have shown that exenatide is well-tolerated in patients and may slow Parkinson’s progression. Additionally, lab data in models of MSA and post-mortem data from the brains of people who had MSA indicate that exenatide may have positive effects.

The trial will comprise people who have had an MSA diagnosis for fewer than five years. They will be randomly split into two groups: those who will add exenatide into their care regimen and those who will continue on with their regular medication. They will be monitored for 48 weeks.

The approach — repurposing a medication developed for one disease to treat another — is an innovative way to maximize scarce resources and shave precious time off of the search for new treatments, said Dr. Patrik Brundin, director of VAI’s Center for Neurodegenerative Science and Parkinson’s expert. Brundin’s lab also studies the origins of MSA and is investigating potential new therapies, such as another drug developed to treat diabetes as a possible treatment for Parkinson’s and MSA.

“Although they look different on the surface, many diseases are linked to similar biological pathways. That’s why a diabetes drug has potential to treat neurological disorders like MSA and Parkinson’s,” Brundin said. “Repurposing is another tool for us to work quickly toward life-changing breakthroughs.”

Fortier sees the trial as a bold new step forward in MSA research, bolstered by a collaborative group of organizations that have united to take on a particularly challenging adversary.

“If we are going to be successful, we need more research and we need to bring together people from across the scientific community,” Fortier said. “It’s a calling — to love and care for one another and do our best to help people with MSA.”

The study is funded by the John Black Charitable Foundation in the UK and Van Andel Institute and the Defeat MSA Alliance in the USA. The study is supported by the MSA Trust (UK).

Read more about the trial here.