New research into the cause of a rare, inherited form of Lou Gehrig's disease could offer new avenues of research to find therapies for all forms of this debilitating disease. This ScienCentral News video has more.
"The prognosis indicated that I had between two and five years to live," says O'Neil. Fortunately the disease was unusually slow to affect him, allowing him to keep working for more than 15 years. But finally in 1985 he was forced to stop working as he lost control of his muscles. "I had no energy. I couldn't fulfill my work obligations and I couldn't travel. I was just exhausted all the time," O'Neil remembers. "I could walk a little bit, but gradually I didn't have strength to do anything— to move my hands or my arms or anything like that."
ALS, a rapidly progressive, invariably fatal neurological disease, is one of the most common neuromuscular diseases worldwide. The specialized nerve cells of the spine that control muscle movements in the body selectively die, leading to progressive paralysis. It strikes people mostly between 40 and 60 years of age, but sometimes even younger, and typically more men than women. As many as 20,000 Americans have ALS and around 5,000 Americans are diagnosed each year.
Nerve cells die when the mitochondria become damaged.
A genetic mutation associated with this type of ALS causes the production of a faulty protein that clogs the surface of the mitochondria, disrupting the mitochondria's energy production in these meter-long, muscle-controlling nerve cells of the spine. "The mutant protein binds to the cell powerhouse, this mitochondrion that produces the energy that every one of our cells needs to survive," Cleveland says. "Although [this protein] is in every cell, it only damages mitochondria in the cells that are ultimately going to die from this disease."
Mitochondria are also known to be the 'gatekeepers' of programmed cell death. Cells have within them a mechanism to recognize when they become irreparably damaged, which then triggers a pathway that leads to their own suicide. "The mitochondria contain most of the molecules that govern the balance between life and death," Cleveland explains. "So our hope is that by interfering in that cascade of damage, from this mutant protein that appears in ALS, and the cell death pathways, that we can keep these [muscle-controlling nerve cells] alive for much longer."
Neurobiologist Dr. Serge Przedborski from the Center of Neurobiology and Behavior at Columbia University Medical Center thinks that although the research is interesting, it's too soon to tell if it applies to other types of ALS. "It has the merit to open new avenues and a new way to think about the neurobiology of ALS. and in that sense I think it's very important," Przedborski says. However, "because those types of mutations are only found, so far at least, in a very small group, we have no idea at this point really if, as significant as it can be, whether it may mean anything to the vast majority of our patients."
Cleveland and his colleagues agree there is still work to be done to identify the causes of the more common form of ALS. "The mutation that we have now studied accounts for about two percent of the instances of ALS," Cleveland points out. "Using the genetics as the starting point leads us to propose new therapeutic approaches. And we have every reason to believe that they would be useful in the cases which do not have a proven genetic linkage." They believe that the mitochondria could also be involved in nerve cell death in the more common non-inherited, or "sporadic" form of ALS, shedding new light that Cleveland hopes could be a light at the end of the tunnel for ALS sufferers like O'Neil.