The mystery of why some people develop ALS

Scientists are racing to understand the causes of this progressive disease and are beginning to make progress.

Actor Kenneth Mitchell, who appeared in films such as Star Trek: Discovery and Captain Marvel, passed away on February 24, 2024, after a five-and-a-half-year battle with amyotrophic lateral sclerosis (ALS). In the months before his death, Mitchell had spoken on social media about what it was like living with the disease, also known as Lou Gehrig's disease, named after the American baseball player who was diagnosed with it in 1939.

“It's been a long five years,” Mitchell wrote on Instagram in August 2023. “So much lost, so much gained. It's been an incredibly difficult time, but so many more blessings. At the heart of it all has been friends, family, caregivers and doctors who have come to our family's aid time and time again. So much support, love, care and encouragement. There is so much beauty in that. This disease is so horrible.”

His death was announced by the photographer Bryan Randall passed away He died in August 2023, but three years earlier he had been diagnosed with ALS at age 54. He was the partner of actress Sandra Bullock, whom he met through work while taking portraits at a family party.

Over the years, many high-profile figures, including young and healthy people, have fallen victim to ALS, yet the cause remains a mystery. However, recent research has uncovered some clues. Could we finally begin to understand this devastating disease?

ALS is a motor neuron disease (MND), a debilitating and painful condition in which motor neurons (cells that control voluntary muscle movement) malfunction. Gradually lostPeople gradually lose control over their bodies. A recent review of available data found that this occurs approximately once a year. 5 per 100,000 people In the United States.

The disease affects more men and the average age at diagnosis is around 60, although it can affect people much younger. Most people only survive a few years after diagnosis, but there are notable exceptions, such as physicist Stephen Hawking. Symptoms of MND at age 21 He passed away in 2018 at the age of 76.

The reasons why people develop ALS are complex. 10-15% of people with the disease Passed down in the familyIn these cases, certain gene mutations have been passed down through generations. If one of your parents or ancestors had ALS, it's not certain that you will develop it, but family lore may include a story about your cousin Lucy or your grandfather Joe having had the wasting disease.

However, it turns out that when people develop hereditary forms of ALS, the genes affected are not necessarily the same, even though the outcome may be the same.

For the remaining 85% of people who develop ALS, the cause is even harder to pinpoint. If after you are diagnosed with ALS, no one says, “Your great uncle had this disease,” it is considered a random, one-off event and is called a “sporadic” case. Recent studies suggest that genetic mutations may be part of the cause; however, this probably involves small changes in several different genes, rather than a single dramatic, obvious biological mistake as seen in familial ALS. Changes in up to 40 genes are thought to be associated with an increased risk of sporadic ALS, but the disease is very rare.

Depending on the type of ALS, “genetic factors explain only about 8% to 60% of the disease,” explains Eva Feldman, a professor of neurology at the University of Michigan.

But it is repeated, Long-term exposure to potential triggers The possibility that the external environment may increase the risk of developing ALS, particularly sporadic ALS, prompted Feldman and his colleagues to conduct their research.

“We suspected the existence of what we call an ALS 'export' — the sum of toxic environmental exposures that increase risk,” Feldman says. The team found that long-term exposure to organic chemical pollutants, metals, pesticides, particulate matter in construction dust, and poor air quality may contribute to the development of ALS. Increases the risk of ALS.

Neil Thakur, Chief Mission Officer ALS AssociationHe says there is no perfect causal relationship with ALS. “It's always a combination of factors,” he says. “Even if you have risk factors or a genetic profile, you're not 100% sure that you're going to develop ALS.”

but, Diesel fuelaviation fuel, particulates Incinerator, Pesticides He added that aerosols may also increase the risk of developing ALS — military personnel, for example, are highly exposed and appear to be more susceptible to contracting the disease, he said.

Also, lead In your drinking water smoking Contact sports may cause ALS. Yet, much uncertainty remains. Studies evaluating the effects of alcohol use and smoking throughout the lifespan before an ALS diagnosis suggest that abstinent nonsmokers may be able to cause ALS. It doesn't necessarily protect you(Of course, there are plenty of other reasons to restrict your diet, as these factors also reduce the risk of developing many other diseases. Drinking and smoking.

One of the challenges faced by scientists and clinicians studying the causes of ALS (and MND in general) is that these diseases are, thankfully, rare. With small numbers of patients, not everyone is willing or able to take part in studies. Also, genetic or lifestyle differences may be influencing the results. For example, even if a genetic change is found in 4% of cases, there may not be enough people in that group to see clear differences between people exposed to a particular chemical pollutant and those who were not.

“It takes a long time to recruit enough people for clinical trials for ALS because the disease progresses quickly and you are only eligible to participate in the early stages of the disease,” Thakur says. “If you have a family history of ALS and you carry the ALS gene, you can see if you can participate in a clinical trial, which could help not only yourself but others.”

Feldman also said studies looking at the combined risk of genetic and environmental factors are “challenging” because he suspects that dozens, possibly hundreds, of genes contribute to what he calls a “polygenic risk profile” for ALS. This risk profile occurs “in addition to the traditional risk from a single gene,” Feldman said. The team is now investigating how this polygenic risk profile interacts with environmental factors to cause ALS.

There is currently no cure for ALS. However, the Food and Drug Administration has approved several treatments to help treat ALS. Slow down They slow it down and give people a little more time. These drugs Mechanism scopeThis has a range of effects, from lowering levels of certain chemicals around the brain and spinal cord to preventing the death of nerve cells.

It also seems possible that treatments that target the effects of specific defective genes may be useful. Recent early trials of drugs designed to counter the damage caused by SOD1 mutations have shown that some Promising Preliminary Resultsfor example.

Knowing which genetic mutation caused the ALS diagnosis may not be particularly comforting for those who currently have ALS. Support and guidance For those suffering from this disease and their families.

“The ALS Association's strategy is to keep people livable until a cure is found,” Thakur said. The association advocates for high-quality care involving medical professionals from a variety of backgrounds, which he said would allow patients to lead more active lives for several months. The association also plans to release guidelines on how to reduce the risk of underlying factors that lead to ALS, he said.

But the challenge is funding for proper research. More work is needed not only to determine the extent to which genes and environmental factors each contribute, but also how to apply the knowledge gained. “The real question is not why people develop ALS, but what can we do to prevent or treat it,” says Thakur.

Whatever the cause, this Progressive disease Family and friends need to respond with love and patience as the situation worsens. Sandra Bullock isHowever, a better understanding of the science behind this devastating disease may lead to the development of more effective treatments and perhaps even one day prevent new cases from occurring, which is always a welcome thing.

*This article was first published on August 27, 2023. It was updated on February 26, 2024 to include details of Kenneth Mitchell's death.