Andrée-Anne, PhD student
Laval University
Parkinson Canada/FRQS Partnership
Graduate Student Award
Amount awarded over 2 years: $20,000

Neuroprotective and anti-inflammatory effects of hormone modulation treatment of the enteric nervous system in Parkinson’s disease

The intricate features of the gastrointestinal system are so sophisticated that medical researchers refer to this as the body’s “second brain.” That description may be especially appropriate for researchers examining Parkinson’s disease, since it is likely this condition may originate in the gut and emerge through digestive problems rather than the better-known symptoms involving stiffness, tremors and other movement disorders.

“There are a lot of non-motor symptoms that might appear as early as 20 years before motor symptoms emerge,” says Andrée-Anne Poirier, a doctoral candidate and researcher at Laval University. “That’s why we think that the disease begins in the periphery before the brain.”

Poirier believes Parkinson’s disease may begin to kill dopamine-producing brain cells after a pathogen or environmental toxin enters the intestinal tract, initiates the disease process and then moves to the brain through the vagus nerve. The vagus nerve is the longest cranial nerve and extends from the abdomen to the brainstem.

Poirier’s work focuses on a dense layer of nerve tissue surrounding the gut, called the myenteric plexus, which can be afflicted with the same problems Parkinson’s disease generates in the brain. Research conducted over the last decade has shown that the female hormone estrogen can protect nerve cells from this kind of damage, but the treatment often leads to serious side effects such as breast cancer and stroke.

Poirier has been investigating ways to create this neuroprotection without the side effects. The search has led her to test raloxifene, a drug initially approved by Health Canada to treat osteoporosis in menopausal women.

Raloxifene works by binding to a hormone receptor called GPER1, which mediates neuroprotection without estrogen’s side effects. This property makes it a promising candidate to treat Parkinson’s disease.

In 2016, Poirier was lead author on a paper that outlined the role this drug could play in preventing the spread of Parkinson’s disease at its earliest stages by protecting more peripheral sections of the nervous system before this condition makes its way to the brain.

Moreover, her work also shows that raloxifene inhibits inflammation in the gut. Inflammation has also been linked to the dopamine-generating brain cells that affect motor control. “We have already been able to demonstrate in the laboratory how we have stopped the inflammatory process that inflicts damage to dopaminergic neurons,” she explains.

Poirier will pursue her doctoral studies by investigating other drugs that are already available but haven’t yet been tested to see if they can treat the early events involved in the initiation and stop the progression of Parkinson’s disease.

For Poirier, the body’s “second brain’ is now being the first line of defense against Parkinson’s disease.