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| Science & Technology |
| The mystery of why some people develop ALS |
| 2026-02-20 |
| [BBC] Scientists are racing to find out what causes this progressive disease. And they're starting to make some headway. After five and a half years of living with amyotrophic-lateral sclerosis (ALS), actor Kenneth Mitchell – who appeared in the films Star Trek: Discovery and Captain Marvel – died on 24 February 2024. In the months leading up to his death, he had described on social media what it was like living with the disease, which is also known as Lou Gehrig disease after the American baseball player who was diagnosed with the condition in 1939. "It's been a long five years," wrote Mitchell in an Instagram post in August 2023. "So much lost, so much gained. Incredibly hard times, mixed with so many more blessings. At the heart of it all are friends and family, caregivers and doctors coming to the aid of my family over and over and over again. Giving a plethora of support and love and care and encouragement. There is so much beauty in that. This disease is absolutely horrific." His death came just a few months after news that photographer Bryan Randall had died in August 2023, who had been diagnosed with ALS three years earlier at the age of 54. He was the partner of the actress Sandra Bullock, who met him on the job while he was taking portraits at a family party. In April 2025, American actor Eric Dane – who starred in Euphoria and Grey's Anatomy – revealed at the age of 52 that he had also been diagnosed with ALS. Despite claiming numerous high-profile victims over the years – including young, otherwise healthy people – the mystery of what causes 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, including the physicist Stephen Hawking who was diagnosed with a form of MND at 21 and died in 2018 at the age of 76. 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. COMPLEX GENETICS There is quite a long list of the genes that can be affected, but there are four main ones. The most common is C9orf72 which is involved in regulation of nerve and muscle cells. The changed gene is found in 30% of ALS cases. In 20% of cases, the fault in is the SOD1 gene, which codes for an antioxidant enzyme which protects cells from damage. A smaller proportion are accounted for by changes in the TARDBP (4%) and FUS (5%). Both of these genes code for key factors involved in making proteins within the cell. 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. Neil Thakur, chief mission officer of the ALS Association, says there is not a complete cause and effect for ALS. "It is always a combination of factors," he says. "Even if you have a risk factor or the genetic profile, it is not 100% sure you will get ALS." But there is some evidence that exposure to particulates from diesel fuel, aviation fuel, particulates from burn pits, pesticides and aerosols may increase someone's risk of developing ALS, he adds. Military personnel, for example, are highly exposed to these and seem to have an increased chance of contracting the disease, he says. There's also evidence that having lead in your drinking water, smoking and contact sports might trigger ALS. Still, there remains a lot of uncertainty. Studies assessing the effect of alcohol intake and cigarette smoking over a lifetime before an ALS diagnosis suggest being a teetotal non-smoker does not necessarily protect you. (These factors do reduce a person's risk of developing many other conditions, of course – so there are plenty of other reasons to limit your drinking and smoking.) One of the challenges that scientists and clinicians investigating the causes of ALS (and MND overall) face is that they are, thankfully, rare diseases. Within the small number of patients, not everyone is willing or able to take part in research studies. And there are many differences in genetics and lifestyle that could be influencing the results. Even if a genetic change is found in 4% of cases, for example, there might not be enough people in that group to see a clear difference between those who have been exposed to a specific chemical pollutant and those who have not. "It takes a long time to fully recruit enough people onto an ALS clinical trial, because the disease progresses so rapidly and people are only eligible early in the disease," says Thakur. "If you do have ALS in your family and you have an ALS gene, you can explore whether you could participate in trials, which would help you and others." |
| Posted by:Skidmark |
| #1 |
| Posted by: Skidmark 2026-02-20 09:13 |