The brain’s lymphatic system and therapies to prevent Parkinson’s disease

Dr. Naomi Visanji
Scientific Associate
Edmond J. Safra Program in Parkinson Disease,
Toronto Western Hospital
Pilot Project Grant
Funded by Pedaling for Parkinson’s in honor of Don MacLean
$49,488.76 over 1 year
Dural lymphatic vasculature: a new player in the pathophysiology of Parkinson’s disease

Many researchers are drawn to studying the brain because they’re still making basic discoveries about how this mysterious organ works. One of those recent discoveries may be key to deciphering the causes of Parkinson’s disease.

Most organs in the body have a lymphatic system to drain toxins, waste and other unwanted materials. After long believing it did not exist, researchers have realized the brain, too, has a lymphatic system to do this cleansing work.

At Toronto Western Hospital, Scientific Associate Naomi Visanji, a neuroscientist, immediately saw the implications of this discovery. She’s investigating the lymph vessels in the brain to see if they do—or could—drain alpha-synuclein, a protein that accumulates in the brain cells critical to Parkinson’s disease. That accumulation kills the brain cells producing dopamine, the chemical that signals other cells to initiate movement.

“Because lymph vessels are involved in drainage of fluid, waste and other unwanted material, it’s a natural idea that the vessels might be involved in the drainage of excess toxic proteins in the brain,” says Visanji.

Using imaging equipment, Visanji will compare the brains of two mouse models. One has been genetically engineered to remove its lymphatic vessels in the brain; the other is a normal mouse.

“Because lymph vessels are involved in drainage of fluid, waste and other unwanted materials, it’s a natural idea that the vessels might be involved in the drainage of excess toxic proteins in the brain.”

After injecting the brains of both mice with alpha-synuclein, Visanji will scan them to see which is clearing the alpha-synuclein, and how fast. She expects to see the alpha-synuclein cleared more slowly in mice without the lymph vessels.

Visanji will then check the vessels for signs of alpha-synuclein. If she finds the protein, it would demonstrate the role these lymph vessels may play in clearing it from the brain. In addition, she’ll study the mice once alpha-synuclein has been injected to see if the symptoms of Parkinson’s disease develop more rapidly in the mice lacking lymphatic vessels.

The next question—requiring a further study—is whether these vessels are damaged in people with Parkinson’s disease.

“One natural hypothesis would be if these vessels are blocked or impaired, perhaps that prevents the alpha-synuclein from being cleared from the brain,” Visanji says.

Visanji’s goal is to produce findings that lead to a new drug or therapy targeting these vessels, which could treat or even cure Parkinson’s disease.

A self-described “science geek,” Visanji is driven by the conundrum that “our own brains aren’t smart enough yet to figure out how they themselves work,” she says.

Long after she began her research in Parkinson’s, her mother was diagnosed with the disease. Now her academic interest has turned into a personal quest.

“Parkinson’s is not just an interesting scientific question, it causes immense human suffering and there’s a big need to work to end that.”