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Extending life for ALS sufferers
Amyotrophic lateral sclerosis (ALS) -- also known as Lou Gehrig's Disease -- is an adult-onset degenerative disease that is characterized by the selective loss of motor neurons. This relentless disease manifests as progressive decline in muscular function resulting in paralysis, speech deficits and, ultimately, death due to respiratory failure within generally 2 to 5 years of clinical onset. ALS affects about two thousand Canadians at any given time and it kills on average three people a day in this country. A recent McGill study offers new hope for ALS sufferers.
PHOTO: Claudio Calligaris
Drs. Jean-Pierre Julien and Jasna Kriz of the MUHC Research Institute have discovered that minocycline -- an antibiotic often prescribed for acne -- can significantly improve the life expectancy in mice that are genetically modified to develop ALS. "The only drug approved presently for ALS treatment is riluzole, and this drug only extends patients' life by three months. That's all there is for ALS patients, there's nothing else, there's no cure," said Julien. Although the disease is characterized by degeneration of motor neurons within the brain and spinal cord, this research team decided to look at a different therapeutic target.
"In the past few years, it became evident that the disease in ALS mice was not just intrinsic to motor neurons, but there was good evidence that there were other types of cells involved in the degeneration processes," said Julien.
"Specifically, we looked at a type of cells called microglia. They're the equivalent of white blood cells, they destroy debris in the brain -- they can play a very beneficial role. But sometimes, when these cells sustain an activation, they can also be damaging and create a toxic environment for the nerve cells."
Following a report a few years ago by a Finnish group that minocycline had beneficial effects in animal models of stroke, probably through attenuation of microglial activation, Dr. Jasna Kriz, a postdoctoral fellow in Julien's lab, initiated a study to test this widely available drug in mice models of ALS.
"Without her coming here I don't think we would have tried working with this compound," said Julien.
The ALS mice only live 48 weeks but when fed with a diet containing minocycline they lived five weeks longer. That represents an improved life expectancy of more than 10 percent. Microscopic examination of the nerves at 46 weeks old revealed remarkable preservation of motor neurons in minocycline-treated mice as compared to controls -- Julien points to slides that show nearly healthy treated neurons contrasted with obviously blighted and diseased untreated brains.
"You don't have to be an expert to see that difference," said Julien.
The University of New Mexico is already planning a clinical trial for human ALS, and Julien expects that there will be trials in Canada as well. As the drug is already available for human use the approval process is moving somewhat quicker than normal. He explained that the pathology in ALS mice resembles very much the pathology in human ALS. Therefore, it seems reasonable to assume that minocycline will confer protective effects in ALS patients. Yet, he cautions, until clinical trials are done we won't know to what extent the drug may slow down disease in humans.
Julien doesn't see this discovery as leading towards a cure, but he does believe that new therapies could possibly change the course of the disease.
"One approach we would like to do, which we are working on presently, is a cocktail approach combining different drugs and different targets," he said. As ALS is a late-onset disease -- generally afflicting people from 45-60 years of age -- to extend life expectancy with a "cocktail" approach would be a victory.
"If you're talking about someone who's 65 years old, and you extend their lifespan by 20 years, then you've beat it," he said.
But even though minocycline may not be a cure, it represents something almost as valuable, according to Suzanne Lawson, National Executive Director for the ALS Society of Canada, which helped fund Julien's research.
"This breakthrough research provides hope, where there had been little, to those who are living with ALS and their families," she said.