MYSTERIOUS KILLER
TheStar.com - Health - Gehrig's discovery sparks hope
Gehrig's discovery sparks hope

TORY ZIMMERMAN / TORONTO STAR



Chita Lontoc, with fingers debilitated by Lou Gehrig’s disease, wipes away tears during an afternoon of prayers with friends and family. The former bank manager is one of 3,000 Canadians living with ALS and for whom a scientific breakthrough holds hope of a cure and treatment for the disease.


Toronto researchers' antibody marks an important breakthrough in battle against Lou Gehrig's disease

Sep 04, 2007 04:30 AM
CHRISTL DABU
Toronto star

Hunched over her microscope at the University of Toronto, Janice Robertson is focused on innocuous-looking brown blobs.

She's been hunting for life-saving clues into the mystery of amyotrophic lateral sclerosis (ALS), the muscle-destroying killer known as Lou Gehrig's disease.

It has perplexed researchers for nearly 140 years and it is a mystery that has captivated Robertson as she watches the microscopic round cells – motor neurons in minuscule sections of human spinal cord and brain.

In ALS, these motor neurons are killed by mutant genes that make defective proteins, she explains, causing paralysis and death usually within five years.

Named for the New York Yankees player killed by the disease in 1941, Lou Gehrig's has also laid waste to physicist Stephen Hawking and claimed the lives of Sesame Street director Jon Stone, jazz legend Charlie Mingus, actor David Niven, composer Dimitri Shostakovich, and Chinese Communist leader Mao Zedong.

Effective treatment and a cure do not exist.

But Robertson and a Toronto team of scientists have developed the world's first antibody to the abnormal protein derived from the mutant superoxide-dimutase-1 (SOD1) gene, the only known cause of Lou Gehrig's, and responsible for 2 per cent of all cases. This antibody could be used to detect and remove the abnormal forms of the protein.

The scientists say their findings, published in the June edition of Nature Medicine, open the door to ways for better treatments, prevention and earlier diagnosis.

In the UofT lab established four years ago by Robertson – at the Centre for Research in Neurodegenerative Diseases – the Scottish molecular cell biologist, working with researchers from UofT's Faculty of Medicine, helped create the antibody using human tissue and transgenic mice.

Their work did not re-invent the wheel but, instead, used and expanded a 10-year-old mouse model.

Previous studies have shown promising results for medication given to the mice that were specially engineered with the mutant SOD1 gene that causes a familial (inherited) form of ALS.

"The thing is, none of the treatments that have been tested in mice has had any effect on humans," says Robertson.

With the shortcomings of the mouse studies, researchers now are also turning their focus on human tissue, something Robertson says was critical in their recent antibody discovery. Unlike the mouse studies, which are only a model for familial ALS, human tissue also allows researchers to study the sporadic forms of the disease that make up the majority of cases.

Robertson, meanwhile, has also joined forces with another team of experts from UofT and Sunnybrook Health Sciences Centre. Her group is among the few in the world to combine a collection of human tissue and blood samples with a comprehensive clinical database for ALS research.

"In a patient with a disease like diabetes, you can perform a blood sugar test for diagnosis. We don't have a biomarker like that in ALS and we're searching for it in the blood or in the cerebrospinal fluid," says Dr. Lorne Zinman, a neurologist who is part of the new ALS research team. He's also medical director of Sunnybrook's ALS clinic, one of the largest in Canada, where on average two ALS patients die from the disease every week.

Their comprehensive approach, they hope, will further the discovery of proteins and genes associated with ALS. To get there, they've been requesting the consent of Sunnybrook ALS patients to collect blood samples and cerebrospinal fluid, as well as their brain and spinal cord immediately after death.

Setting up ALS patient databases has now become the priority in Canada, the U.S., Australia and Europe.

"In Toronto, they're trying to take it a step further," says Dr. Robert Bowser, director of the Center for ALS Research at the University of Pittsburgh School of Medicine.

"That would be quite valuable and critical to other institutions, and will greatly facilitate finding a cure for ALS."

A cure is what Chita Lontoc, of Toronto, is praying for. She sits on her wheelchair in her east-end home, clad in blue pajamas. In her lap rest her hands, freshly manicured – something she still has done every three weeks. Every five weeks she has a facial. Every six weeks, she has her hair dyed hazelnut.

"I still want to maintain my vanity," laughs the 55-year-old former bank manager.

But life really isn't as it used to be. In October 2005, she joined the 3,000 Canadians who live with ALS. Every day, she watches her body crumble a little further. She can no longer do most daily tasks, like button her shirt, bathe or use the toilet, and has a full-time caregiver.

And every day she worries, mostly for her sons, Jayme, 27, and Raymond, 21. Doctors told her that her siblings and children have a 50 per cent chance of developing Lou Gehrig's disease. Lontoc's father also had ALS and died at age 68, almost 20 years ago.

She is now pinning her hopes on research.

"It's hope for future generations, hope there's something that can cure the disease," says Lontoc.


Back at her third-floor office at UofT, Robertson notes that Rilutek, which mildly slows the disease's progression, is the only medication approved to treat ALS. Currently, 14 clinical U.S. trials are testing ALS medications.

"We're hopeful," she says of the ultimate goal of finding a cure. "But at the moment if you are asked (by a patient), `What are you doing for me?' it kind of gets you because ... you could do a lot more if you had more money," says Robertson.

"But we're able to begin. We're determined to do it ... because these people are desperate – they're dying."

http://www.thestar.com/living/article/252719