ALS Nerve Fuel

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.

Power-full New Research

"We have known that the neurons that connect to the muscles selectively die, but we have been perplexed as to what gives rise to their early death," explains neuroscientist Don Cleveland, Director of the Laboratory of Cell Biology in the Ludwig Institute for Cancer Research at the University of California, San Diego (UCSD). Now Cleveland and a team of researchers from UCSD, Johns Hopkins University and elsewhere may have discovered why this happens in one rare, inherited form of ALS. They found that the nerve cells die when structures called mitochondria— the powerhouses of the cell— become damaged.

Nerve cells die when the mitochondria become damaged.

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.

This research appeared in the July 8, 2004 issue of the journal Neuron. It was funded by the National Institutes of Health, the ALS Association and The Ludwig Institute for Cancer Research.