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Leading-edge technology allows Sunnybrook researchers to discover brain diseases sooner, so that treatment will be more effective. Dr. Sandra Black, director of the Hurvitz Brain Sciences Program at Sunnybrook Health Sciences Centre, and Dr. Peter Kertes, chief of ophthalmology, team up to look inside a patient’s eye for signs of amyloid buildup, an early harbinger of dementia. (Doug Nicholson)

Leading-edge technology allows Sunnybrook researchers to discover brain diseases sooner, so that treatment will be more effective. Dr. Sandra Black, director of the Hurvitz Brain Sciences Program at Sunnybrook Health Sciences Centre, and Dr. Peter Kertes, chief of ophthalmology, team up to look inside a patient’s eye for signs of amyloid buildup, an early harbinger of dementia.

(Doug Nicholson)

Game-changing global trials could slow down Alzheimer’s Add to ...

The race is on to prevent one of the most debilitating diseases of our time

When the diagnosis finally came, Oshawa residents Carol Browne and her husband, Mike, were “shocked and devastated” to hear the words “early-onset Alzheimer’s.”

The couple had known for a while that something was seriously wrong. Ms. Browne, an RBC employee in her early 50s, was beginning to struggle over simple tasks such as balancing her chequebook and even just writing.

“The first time I really noticed there was a problem,” Ms. Browne recalls, “I was at work and trying to write a w.” She couldn’t form the letter. At the time, it didn’t worry her a whole lot, but it wasn’t long after that incident when she worsened. She was 56 years old when she was diagnosed with early onset Alzheimer’s by neurologist Dr. Sandra Black, director of the Hurvitz Brain Sciences Research Program at Sunnybrook Health Sciences Centre.

According to the Alzheimer Society of Canada, about 500,000 Canadians suffer from the disease, a progressive and degenerative one that destroys brain cells. Alzheimer’s is the most devastating and common form of dementia, a group of illnesses characterized by memory loss. The society predicts that, by 2038 the number of people with Alzheimer’s will have more than doubled, to 1.2 million, costing the economy $153-billion a year.

That’s why the race is on globally to slow down or even prevent onset of the disease.

Sunnybrook researchers Dr. Black and Dr. Mario Masellis are focused on studies that, if successful, will be game changers in the fight against Alzheimer’s. Their work is part of Sunnybrook’s Hurvitz Brain Sciences Program, which takes an unprecedented approach to collaboration, linking experts in each field of brain sciences – including psychiatry, neurology, pharmacology and geriatrics – in an effort to accelerate research and slow the progress of brain disorders.

“Once a person develops Alzheimer’s, there are therapies that can help, but they don’t target the underlying cause,” explains Dr. Masellis. “The studies being proposed now go after the root cause of the disease, because once symptoms start, drugs are less effective.”

In international trials (see “The DIAN trial,” right), the goal is to take participants who are at high risk of developing the disease and see if it can be delayed or stopped by using drugs that target what scientists believe is a cause of the illness.

We have known for a long time that the disease starts in the brain in the 30s or 40s, and the markers are there. So, the
point is to get to it much earlier."


Dr. Sandra Black,
director of the Hurvitz Brain Sciences Research Program
at Sunnybrook Health Sciences Centre


A working theory that’s been around for many years is that a toxic protein produced in the brain, called amyloid, gathers and clumps together in a gluey mass, causing neurons to die.

An international trial called A4 will aim to uncover whether getting rid of amyloid can help slow the memory loss associated with its buildup. The A4 trial will begin in the next six months and span three years, during which time participants will receive either the experimental drug or a placebo.

Dr. Black explains that the people in the trial will not be afflicted with Alzheimer’s.  However,  they will be at risk of getting the disease. “We will give them an amyloid scan and if it shows uptake in critical areas, we will offer the treatment monthly over three years and see if it will prevent the development of symptoms,” she says.

Success would be a “game changer,” Dr. Black contends, as the treatment would become the first therapy to slow down the progression of amyloid and the onset of dementia, well before a patient experiences symptoms or is diagnosed. It would also confirm that amyloid is indeed a key factor in dementia.

The internationally renowned researcher likens the urgency of treating amyloid to that of treating cancer and getting to a tumour at an early stage before it spreads and becomes incurable.

“We have known for a long time that the disease starts in the brain in the 30s or 40s, and the markers are there. So, the point is to get to it much earlier,” says Dr. Black. “The reason it is intriguing is because we are trying to treat people when amyloid is relatively manageable. We have dared to go into the pre-stage of Alzheimer’s in a serious way. Ten years ago this would not have been possible.”

Looking to the future, if the trial shows beneficial effects, it would be possible to screen people with brain scans and find out if they are at risk of developing the debilitating illness.

“The question then becomes: Can we afford to make this widely available?” says Dr. Black. “Perhaps we can’t afford not to.”

Besides aging, other risk factors for Alzheimer’s include high cholesterol, high blood pressure, obesity and a sedentary lifestyle. The neurologist points out that we can take steps to try and keep our brains healthy.

“If you are lucky enough to be actively using your mind on a daily basis and eating good food, then that’s protecting your brain. Physical exercise and not smoking or drinking also helps to keep the brain healthy.”

Since the day they sat in Dr. Black’s office, life has changed dramatically for Carol and Mike Browne, who’ve been married for more than 40 years.

There was a time when they were planning their retirement together, but now they sign up for drug trials, go to support meetings and visit Sunnybrook regularly. They remain hopeful there will be a breakthrough in their lifetimes. Both agree the hospital provides a high level of compassionate care.

“Sunnybrook has been wonderful. I like going there,” says Ms. Browne with a laugh. “There’s always someone there to greet and help you.”

 

The DIAN trial
The Dominantly Inherited Alzheimer Network (DIAN) is an international research partnership of leading scientists determined to understand a rare form of Alzheimer’s disease caused by a gene mutation. The DIAN trial targets younger patients who have a genetic mutation and are either guaranteed to eventually get the disease or have a 50-50 chance. The DIAN trial’s goal is to identify and treat Alzheimer’s very early, before the symptoms are apparent. “This is a rarer form of Alzheimer’s but equally as severe for those who get it,” Dr. Mario Masellis, neurologist, Hurvitz Brain Sciences Program says. “It’s even more serious from a sociological prospective, as these are people in their 40s and 50s.” Participants in the study will include people at high risk of acquiring the disease because of the genetic factor and, to qualify for inclusion in the trial, should be within about five years of when the family member was diagnosed. “For those with a family member who has the disease, there is a 50 per cent chance of their having the mutation,” Dr. Masellis explains. “There is a genetic test they can take to know what their risk is. But not everyone wants to take it.” Though extremely rare, early onset Alzheimer’s is one of the reasons why the amyloid theory has become so prominent. “These mutations are in genes that are linked to amyloid. Amyloid discovery was in part made because of this,” Dr. Masellis says. “We can see the changes in the brain under the microscope.”


This is the fourth in a six-part series about the future of brain sciences. Look for the next article on Thursday, March 5. Visit sunnybrook.ca/brain for more information.

 


This content was produced by The Globe and Mail's advertising department, in consultation with Sunnybrook. The Globe's editorial department was not involved in its creation.

 

 

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