(RxWiki News) Exercise may slow the degenerative death march caused by Amyotrophic Lateral Sclerosis (ALS), better known as Lou Gehrig's disease.
University of Alberta researchers, led by Dr. Kelvin Jones (winner of this year's ALS Canada Discovery Grant) have studied mice genetically altered to display familial ALS and found that exercise slows the disease considerably. ALS is a motor neuron disease characterized by muscle weakness and atrophy. Life expectancy is two to five years after diagnosis, though some patients live 10 years or longer.
"Exercise in mice showed a beneficial effect," said Jones, a professor in the Faculty of Physical Education and Recreation. "We have been looking at the rate of denervation of the muscles to see how quickly the disease progresses and the muscles weaken."
He called the findings "very encouraging."
Jones implanted a tiny pacemaker-like device in the mice to stimulate so-called fast-twitch muscles, which are those that fatigue easily, such as a sprinter would use during a short burst of speed. Slow-twitch muscles are designed for endurance, such as those of a marathon runner. The muscles are well-vascularized with more myoglobin (an oxygen-carrying protein found in human muscle).
Stimulating fast-twitch muscles by passively exercising the mice, Jones found they transformed to slow-twitch muscles, the kind built for endurance. This resulted in a delayed progression of ALS in the mice.
Fast-twitch muscles are more vulnerable to degeneration in ALS.
"If you have ALS, the more of the fast-twitch muscle fibre you have, based on the mouse studies, the quicker the symptoms (of ALS) come on," said Jones. "(We think) if we try to build more of the slow-twitch muscle fiber in ALS patients, it would slow the progression of the disease."
Jones is ready to test the findings to a clinical trial in humans. There have been few exercise trials in ALS research since many neurologists believe exercise exacerbates the disease (since ALS patients have more of the vulnerable slow-twitch muscles that degenerate first).
Meanwhile, a team at Brandeis University has expanded on recent research uncovering a gene that causes familial versions of the disease. In the study, researchers studied mutations in the gene that makes a particular protein (SOD1) unstable, causing it to fall apart into two identical pieces.
Chemist and study author Jeff Agar put the research in laymen's terms: "Picture a tennis ball stuck to a small piece of double sided tape. Now picture another ball. Turn the balls until both pieces of tape come into contact, and that's what scientists call a dimer, and it's stable. It won't stick to anything else. That's what normal SOD1 looks like, and there are billions of SOD1 dimers in every motor neuron. Now pull the tennis balls apart, turn one ball 180 degrees, stick them back together, and there's a sticky end. That's what ALS-associated SOD1 mutants do. You could stick millions of these balls together if you had them, and a neuron has billions of them. ... What we're trying to do is prevent this from happening."
To address this, Agar and colleagues developed a so-called "chemical rope" to tie the two monomers together, creating a stable dimer.
The familial variant of ALS affects only about 2 percent of patients with the disease, but researchers believe maybe 30 percent to 40 percent of cases where there is no genetic cause could potentially also benefit from the same treatment.