New cellular model for Parkinson’s

Dr. Janelle Drouin-Ouellet
Professor
University of Montreal
New Investigator Award
$90,000 over 2 years
Understanding mitochondrial dysfunctions in sporadic Parkinson’s disease using direct neural reprogramming of patient-derived dermal fibroblasts

Until now, most researchers studying Parkinson’s disease have used animal models or models derived from stem cells to investigate the cause of this neurodegenerative disease, and ways to treat or prevent it.

Neither method, though, provides an accurate way of studying age as a risk factor for Parkinson’s disease. That’s why Professor Janelle Drouin-Ouellet, a neurobiologist at the University of Montreal, has contributed to developing a new technique that converts skin cells into brain cells. The technique is called direct neuronal reprogramming.

“What’s very important about this technology is that the brain cells in a [petri] dish are maintaining the aging signature of the skin cells, meaning that if the donor is 80 years old, the brain cells in the dish will be 80 years old,” Drouin-Ouellet says.

Having a variety of “aged” brain cells will enable Drouin-Ouellet to study the age at which survival systems within brain cells begin declining, and the reasons mitochondria – the organelles within cells that make them breathe – are malfunctioning, causing brain cells that produce dopamine to die.

“There aren’t any models in the lab to study the aging aspect of Parkinson’s. That’s what I’m bringing to the table,” she says.

Using 20 different lines of patient cells that produce dopamine, the brain chemical that’s crucial in Parkinson’s, Drouin-Ouellet will expose them to different potential causes of the disease. For example, she’ll expose some cells to a pesticide associated with Parkinson’s, and others to a protein called alpha synuclein, which causes brain cells to die when too much of the protein clumps together.

“There aren’t any models in the lab to study the aging aspect of Parkinson’s. That’s what I’m bringing to the table.”

 Drouin-Ouellet will compare how the mitochondria within the dopamine- producing cells donated from people with Parkinson’s cope with these stresses, compared with cells from healthy donors.

By pinpointing the ways cells respond, Drouin-Ouellet hopes ultimately to identify subgroups of Parkinson’s disease with different causes. Some people might have mitochondrial impairment; others might have a more severe protein build up, and that might occur at an older age than the mitochondrial dysfunction.

She believes identifying the causes could lead to personalized medicine, so that people whose Parkinson’s disease is caused by one cellular process could receive a different drug or treatment than people whose Parkinson’s is caused by a different cellular process.

“It will improve the quality of treatment if we can tailor therapies to a specific sub-type of Parkinson’s,” Drouin-Ouellet says.

Drouin-Ouellet spent five years improving this new technique in cell conversion, because she believes synthetic biology “is the future.” She likes a challenge, and has known since she was 16 that she wanted to be a researcher in the medical field.

Today, she also has another important motivation for working in the field: her grandmother, Ghislaine Bouchard, has recently been diagnosed with Parkinson’s.