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Q&A — An Unlikely Origin for Parkinson’s disease

Q&A — An Unlikely Origin for Parkinson’s disease

In the early 2000s, German anatomist Heiko Braak put forward a maverick theory to explain what causes Parkinson’s disease. He proposed that rogue proteins made in the gut travel along nerves to kill brain cells. But is the gut really to blame? New research from a team led by Ted Dawson, M.D., Ph.D. — Leonard and Madlyn Abramson Professor of Neurodegenerative Diseases at The Johns Hopkins University and director of the Morris K. Udall Parkinson’s Disease Research Center of Excellence at Johns Hopkins — has found new evidence to support this theory. Experiments on mice show that a misfolded protein — alpha-synuclein — travels up the nerves connecting the brain to the gut. As the proteins spread, they begin killing brain cells in the same pattern that Braak observed. This study, says Dawson, opens new doors for testing treatments for Parkinson’s disease.

Dawson answered the following questions about his research discovery.

What is the gut-brain connection?

The brain is connected to the GI tract through, primarily, the vagus nerve. The vagus nerve starts in the brain stem — the lower part of the brain — and goes down your esophagus and then goes into your stomach and large intestine. It controls the digestive function of the gastrointestinal tract.

What were the results of your research?

We found a way to replicate Parkinson’s disease in a mouse by injecting a pathologic form of alpha-synuclein into the stomach. We showed that the pathologic synuclein kind of rides up the vagus nerve into the brain then. Once it’s in the brain, it spreads from cell to cell to create the symptoms of Parkinson’s disease.

What inspired you to start looking at this?

We were inspired by studies from Heiko Braak in the early 2000s. He proposed that Parkinson’s disease may start in the gastrointestinal tract and ascend up the vagus nerve. He based his hypothesis on patterns of brain damage he observed in autopsies of the brains of people with Parkinson’s disease. We’ve now created an animal model to directly test his hypothesis.

What is the importance of having an animal model?

Prior to this animal model, we were limited to studying the motor features of Parkinson’s disease: the slowness of movement, rigidity and tremor. We now have a model that exhibits almost all of the features of Parkinson’s disease observed in humans, ranging from gastrointestinal dysfunction to motor dysfunction to anxiety and depression.

What’s next, and what can we do with this information?

With this model, we can study what clinicians call the nonmotor features of Parkinson’s disease. These include anxiety, depression and cognitive dysfunction in the context of Parkinson’s disease. We can also use this model to test potential therapies that either prevent or treat the symptoms of Parkinson’s disease.

Is this exciting for the field?

Oh yes, it’s tremendously exciting for the field! I think it’s going to really revolutionize what we do and study in Parkinson’s disease.
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