New ALS vaccine shows promise
Aaron Derfel, The Gazette


Researchers from Quebec and Harvard University are working on a promising vaccine to treat people suffering from Lou Gehrig's disease, the devastating neuro-muscular disorder.

There is no known cause or cure for the disease, known formally as amyotrophic lateral sclerosis. As many as 3,000 adult Canadians live with ALS, and most will die from it within two to five years of its diagnosis.

But there is hope on the horizon since United States neuroscientist Robert Brown identified a genetic mutation in a small percentage of cases of ALS.


Now Brown and researchers from Université Laval, in Quebec City, are developing a vaccine that would target a toxic protein in people with the genetic mutation.

"The particular protein that has been the subject of much discussion is one that is made in every cell of the body in very high quantities," Brown explained yesterday at the Montreal Neurological Institute, which is holding a symposium this week on ALS.

"It's so important that every animal in the world makes this protein. It's a protein that defends against oxidative damage from breathing air."

Yet in people with the genetic mutation, the protein becomes toxic.

"It mutates in a way that causes it to be unstable, misfold and to acquire a very wide number of toxic properties, probably impairing many, many aspects of the motor neurons that will die."

ALS starts when these motor nerve cells die in the spinal cord. Voluntary muscles degenerate and the senses then become impaired.

The idea behind the therapeutic vaccine would be to create in the laboratory antibodies against the rogue protein, then inject them in patients who have the genetic defect and who might be suffering from the early stages of ALS. The antibodies would trigger the immune system to attack the toxic proteins (called SOD1), and spare patients damage from ALS.

Researchers from Universite Laval have already proved such a vaccine is effective in lab mice that have been genetically induced with ALS. The researchers, led by Jean-Pierre Julien, injected eight ALS mice with the vaccine and seven ALS mice with a harmless saline solution.

The study, published in February in the Proceedings of the National Academy of Science, demonstrated the vaccinated mice lived a month longer. In human terms, that would translate into hundreds of days.

Julien is now seeking to "humanize" the antibodies so they can be injected into humans without causing an inflammatory response.

"It's very exciting," Julien told The Gazette. "We're hoping to start clinical trials in two or three years."

Still, a cure is long way off. The genetic mutation in question is present in only 20 per cent of cases of familial ALS. And familial ALS represents less than 10 per cent of all cases of ALS.

The third annual symposium was sponsored by the André Delambre Foundation, in honour of the Quebec entertainment executive who died of ALS in 2006.

What's unique about the symposium is that it draws ALS researchers from the U.S. and Europe, who are willing to share the results of their research even before publication in journals.

Given the intense rivalry in the scientific world, that kind of co-operation is a rare thing, delegates to the symposium agreed.

"Each of us alone is not going to solve this and, really, the real benefit is not the personal ego - the real benefit is the patient," said Stanley Appel, a Houston physician.

aderfel@thegazette.canwest.com

http://www.canada.com/montrealgazett...699c36b&k=7724