Preventing the death of critical brain cells

Preventing dopamine neuron death from oxidative stress to treat Parkinson’s disease

Professor Brian MacVicar was writing a scientific paper about a discovery he and his colleagues made that a giant ion channel on cell membranes called Panx1 is activated by oxygen molecules, when an idea hit him.

What if this channel is the way toxic oxygen molecules kill the brain cells that produce dopamine, the signalling chemical that is critical for movement and central to Parkinson’s disease?

MacVicar holds a Canada Research Chair in Neuroscience at the University of British Columbia. He knows that the death of dopamine-producing brain cells causes Parkinson’s disease, and he’s long been interested in the cell death process.

What neither MacVicar nor any other researcher knows for sure is what causes those brain cells to die, producing the stiffness, tremors and difficulty walking that characterize Parkinson’s.

“I hope that the work will lead to a drug that will reduce or even prevent the death of dopamine-producing brain cells.”

Other research has implicated the generation of toxic oxygen molecules, called reactive oxygen species.

If the Panx1 channel is in brain cells that produce dopamine and is activated by these oxygen molecules, then the channel could be critical to understanding – and potentially stopping – the process that causes Parkinson’s.

“This became obvious as a good thing to test,” MacVicar says.

Using high-resolution imaging and fluorescent dyes, MacVicar and his team will observe what happens when the Panx1 channel opens and how that affects the health of brain cells.

“We’re going to look at the response of the surrounding cells, the microglial cells,” he says.

If the channel does play a role in causing the death of these dopamine-producing brain cells when they get stressed by reactive oxygen, then MacVicar hopes to find a way to block the channel from opening, preventing the cells from dying.

If MacVicar can prove this concept in an animal model, he hopes the work would then move “fairly rapidly” into a clinical trial.

“I hope that the work will lead to a drug that will reduce or even prevent the death of dopamine-producing brain cells,” MacVicar says.

As a child, MacVicar was fascinated by his psychiatrist father’s stories of how the brain works and what happens when things go wrong with the brain. In addition to this work on Parkinson’s, his lab also focuses on basic research into Alzheimer’s disease and traumatic brain injury.

“In each of these conditions, there is a huge component of oxidative stress,” he says.

He hopes his work on the Panx1 channel can ultimately help not only people with Parkinson’s, but those who suffer from these other diseases as well.

How your support made this research project possible

Pilot project grants are important because it is difficult to get funding to explore early ideas, says MacVicar. His research into other diseases led to the point where the question of the involvement of the Panx1 channel in Parkinson’s disease became “kind of obvious,” but it is normally hard to get funding to test an idea quickly.

“Having this funding to perform this initial test is a huge, huge benefit,” he says.

If MacVicar’s idea proves to have merit, he can then turn to other funding sources to explore the implications further.

The funding donors supply is critical because of the length of time it takes to turn basic research into an application that could ultimately improve quality of life and save lives.

It takes years to develop brain analysis techniques and establish a neuroscience lab that has the capability to ask the question and answer it, MacVicar says. “That takes an investment of years and years– and a great team.”