Despite claiming numerous high-profile victims over the years – including young, otherwise healthy people – the mystery of what causes amyotrophic-lateral sclerosis (ALS) remains. However, recent research has uncovered some clues. Could we finally be on track to decoding this devastating condition?
ALS is a form of motor-neurone disease (MND). It is a debilitating and painful condition in which the motor neurons – cells that control voluntary muscle movement – are gradually lost, leading to people slowly losing control of their bodies. A recent review of the available data estimated that it affects somewhere around five people per 100,000 in the US.
The disease occurs more commonly in men and the average age of diagnosis is about 60 years old, though it can also affect people who are significantly younger. While most people live only a few years after the diagnosis, there are notable exceptions.
The reasons why people develop ALS are complicated. For 10-15% of people with the condition, it runs in the family. In these cases, a mutation in a particular gene would have been passed through the generations. It is not certain that if one of your parents or ancestors had ALS, you will develop it as well, although there may be stories about cousin Lucy or grandpa Joe having a wasting illness in the family folklore.
However, it turns out that when people do develop the inherited form of ALS, the affected gene is not always the same one, even though the consequences are the same.
For the other 85% of people who develop ALS, identifying the cause is even less straightforward. When no-one says “your great uncle had something like that” after someone gets a diagnosis for ALS, then it is considered to be a random, one off, event and is called a “sporadic” case. Recent research has suggested that genetic mutations might be part of the story. However, these probably involve little changes in a few different genes rather the single drastic, obvious biological mistakes noted for familial ALS. Changes in up to 40 genes have been implicated in increasing someone’s risk for sporadic ALS, though the condition is extremely rare.
Depending on the type of ALS, “the extent that disease can be explained by genetic factors is only about 8% to 60%,” explains Eva Feldman, a professor of neurology at the University of Michigan.
However, there’s also emerging evidence that repeated and prolonged exposure to potential triggers in the external environment might increase the risk of someone developing ALS, particularly the sporadic form. This led Feldman and her colleagues to investigate.
“We suspected the presence of what we term the ALS ‘exposome’, which is the sum of toxic environmental exposures that increase risk,” says Feldman. The team have found that prolonged exposure to organic chemical pollutants, metals, pesticides, particulate matter in dust from construction work and poor air quality could contribute to increasing a person’s ALS risk. (BBC)
