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Fox drives Parkinson's research back to the future

Thursday September 24, 2009

The Globe and Mail - Canadian actor's foundation taking an aggressive, entrepreneurial approach to science

Michael J. Fox comes to the door of his Manhattan office with a muscular, rambunctious puppy named Gus, a Great Dane/black-lab cross that he concedes is a lot of dog for someone with Parkinson's disease.

“You'd think a guy with Parkinson's who's not as strong as he might have been doesn't really need a 95-pound dog dragging him through the park,” the Canadian-born actor, author and philanthropist says after settling Gus in the reception area with a toy lobster and sitting down on the couch.

Mr. Fox may be best known for his roles in Family Ties, Spin City and the Back to the Future movies, but in recent years he has become the public face of Parkinson's, a progressive, incurable brain disease diagnosed in 1991, when he was 30.

It affects his muscle control and gives him a shaky, uneven gait, but he is confident that by the time five-month-old Gus is big enough to pull him down, he will have invested so much love and time in training him that his pet won't yank him off his feet.

That kind of optimism has defined Mr. Fox since he first went public about his illness in 1998, and Canadians will get a dose of it this week when he comes to Toronto to celebrate the fact that the Michael J. Fox Foundation now has charitable status in Canada.

It is at the heart of his mission to find a cure for Parkinson's by reshaping the way research is done.

Many people remember Mr. Fox's very public battle with the Bush administration to permit research on stem cells (cells derived from human embryos that have the potential to turn into any kind of cell in the body). They may be surprised to learn that today his foundation, in the words of one scientific advisory board member, has reappraised how that research realistically relates to Parkinson's and is focusing on other areas.

But that's typical of the group's aggressive, entrepreneurial approach to science. Staffed with neuroscientists and people with business experience, the foundation has spent more than $149-million (U.S.) on research so far.

The foundation demands that scientists share results and tools, and it closely monitors their work. But it also encourages them to take risks, devoting roughly $2-million a year to a rapid-response fund that gets money quickly into the hands of scientists who come up with new ideas.

In less than six weeks, a scientist can have the seed money to test out a hypothesis and see if it is worth pursing. Most of the time, it doesn't pan out, which is why government funding agencies prefer to support research that will lead to steady but incremental advances.

However, many scientists will tell you that it is this bold style of work that often leads to major discoveries.

Mr. Fox, who dropped out of high school as a teenager but finished as an adult, says funding high-stakes research made sense to him. The methodology grew out his discussions with scientists as he mulled over whether he should get involved with other Parkinson's charities.

“I realized there had to be an element of risk built in, and that it had to be something that came with the velocity of the ideas.”

He also came to see that no one was co-ordinating research efforts in Parkinson's and that there was little funding to get promising results translated into new treatments for patients. His foundation has become that patient-focused control centre.

When he set it up in 2000, he hoped that it would be short-term endeavour and he spoke brashly about finding a cure within a decade. Today, he and the scientists who advise him know that Parkinson's is far more complicated than they initially believed.

“You are driving towards a cure, you are hoping for a cure, but you realize how many huge victories there are on the way to that. In trying to answer the big questions you realize how many small questions there are,” Mr. Fox says.

But he is unfazed by the slow progress, and remains convinced that his foundation's approach offers the best chance of accelerating the pace of discoveries.

“I just know we are doing the right thing, and we are as good at this as it gets. … We would be happy for a quick win, but we are ready to get into the corners and grind.”

Dopamine deficit

People with Parkinson's disease – including an estimated 100,000 Canadians – have damage to an area of the midbrain called the substantia nigra. The cells there produce the chemical dopamine, which allows the smooth, co-ordinated function of the muscles.

No one knows why these cells die in patients with Parkinson's, but researchers are investigating both environ-mental factors, such as exposure to pesticides, and the genes that play a role in the relatively rare inherited cases of the disease. They are also looking for a biomarker – something that will indicate that damage to dopamine-producing cells is occurring.

In 1990, when Mr. Fox found he couldn't stop his pinky finger from twitching and trembling, 50 to 80 per cent of his dopamine-producing cells were already dead.

Andres Lozano, a Parkinson's researcher at Toronto Western Hospital and a founding member of the scientific advisory board at the foundation, says that there are many facets to the challenge. “We want to understand what causes Parkinson's disease, [and develop] novel treatment for symptoms and novel treatment that will change the course of the illness. It is a huge undertaking.”

One of their partners in that effort is Toronto's McEwen Centre for Regenerative Medicine, where researchers are collaborating with other clinicians to see if stem cells that have been coaxed into becoming heart cells or pancreatic cells can help laboratory animals with heart disease or diabetes.

But using stem cells to repair damaged brains is an even more daunting proposition because the organ is so complex and so much depends on how cells connect to one another.

Mr. Fox says he's still convinced that there will a stem-cell breakthrough one day and the research his foundation funds will eventually pay off in new treatments or a cure.

“You can look at a baby and say, ‘How is this ever going to drive a car?'” he says. “You feed and love it and keep it out of traffic. You have to do the work. Obviously you are outcome-oriented, but you realize the outcomes are sought after and need to be achieved all the way up the ladder.”

In the meantime, his foundation is funding research on everything from the growth factors in the brain that help dopamine-producing cells grow to whether exercise can help people with the disease.

“It will take a lot of time, but it's not time-neutral,” he says. “There is an urgency to what we are doing, and regardless of our developing understanding of the realities, we still aren't giving up the urgency.”

Mr. Fox has now had Parkinson's, a disease that usually hits people in their 60s, for almost two decades.

He has had brain surgery, and makes his daily attempt to find the right level of medication to control his symptoms without being overwhelmed by the side effects. His body constantly jerks and spasms in a side-to-side motion throughout the interview in his Upper East Side office. At times, it seems that only his eyes are still, and they convey a sense of calm and focus despite the frenetic movement in his arms and legs.

“I wanted to be as lucid as I could when I was talking to you, so I took more L-dopa [medication to control tremors and other symptoms] than I normally would. The price I pay for that is this movement,” he explains.

“If I erred the other way, then I would be a little halting. I'd have a harder time finding words. I'd be a little more tremulous and tentative. Either way my psyche and my attitude and my emotional status is exactly the same.”

A life beyond limits

Despite his physical limitations, he is still working occasionally as an actor, winning an Emmy for his role playing a paraplegic in the New York firehouse drama Rescue Me.

He is writing another book, his third, which he describes as akin to a commencement speech to college graduates.

He is married to actress Tracy Pollan, and plays an active role in the lives of his three younger children, all daughters. His oldest, Sam, now 20, is at college. He has said many times that he plans to dance at their weddings.

However, the Michael J. Fox Foundation is not about curing his own Parkinson's, he insists. “I don't know if I am the master of compartmentalization, but this is truly not about me.

“I have such a terrific life, a great family, and I have been able to do a lot of things I wanted to do in my life, and I have arrived at a place of relative comfort notwithstanding I have this uncomfortable condition.”

On Thursday in Toronto, Mr. Fox will speak at a press conference and take part in a round-table exchange between people with Parkinson's and top Canadian researchers.

In the evening, he and rocker Bryan Adams will be the star attractions at a fundraising dinner. His 80-year-old mother is coming from British Columbia and his sister will be there. The goal is to raise $500,000, in a joint effort with the McEwen Centre and Toronto Western Hospital.

“I have a sense of purpose,” Mr. Fox says. “If it is like this for the rest of the ride for me, that's fine.

“It is what it is, but I do like to win, and I am convinced we are on the right track and it is worthwhile – regardless of what it means for me personally.”