Scientists are racing to discover what causes this progressive disease. And they are starting to make some progress.
In August 2023, the world was told that Brian Randall had died.
He was a professional photographer and partner of actress Sandra Bullock, who met him at work while taking portraits at a family celebration.
Unfortunately, three years ago, at the age of 54, he was diagnosed with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, after the American baseball player who contracted the condition in 1939.
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Despite the fact that it has claimed many famous victims over the years - including young, otherwise healthy people - the mystery of what causes ALS still remains unsolved.
However, recent research has revealed some new hints.
Could it be that we are finally on our way to shedding light on what is behind this catastrophic state of affairs?
ALS is a form of motor neurone disease (MND).
It is a debilitating and painful condition in which motor neurons - the cells that control voluntary muscle movements - gradually die, causing people to slowly lose control of their own bodies.
A recent review of available data estimated that it affects about five people out of every 100.000 in the US.
The disease occurs more often in men, and the average age of diagnosis is 60 years, although it can also occur in people who are significantly younger.
While most people live only a few years after diagnosis, there are some exceptions, including physicist Stephen Hawking, who was diagnosed with a form of MND at age 21 and died in 2018 at age 76.
The reasons why people get ALS are complicated.
In 10-15 percent of people with this condition, it is hereditary.
In these cases, the mutation of a particular gene is passed down through the generations.
It is not certain that if your parents or another ancestor had ALS that you will also get it, although there may be stories about how cousin Lucy or grandfather Joe had this serious disease according to family tradition.
However, it turns out that when people do get the hereditary form of ALS, the affected gene is not always the same, although the consequences are.
For the other 85 percent of people who develop ALS, identifying the cause is even less straightforward.
When no one says "your great uncle had that" after someone is diagnosed with ALS, then it is considered a random unique event and is called a "sporadic" case.
Recent research has shown that genetic mutations may be part of the story.
However, they probably involve small changes in several different genes rather than the drastic, obvious biological error that occurs in familial ASL.
Changes in up to 40 genes have been linked to an increased risk of sporadic ALS, although the condition is extremely rare.
There is quite a long list of genes that can be affected, but four are the main ones.
The most common is C9orf72, which participates in the regulation of nerve and muscle cells.
The altered gene is found in 30 percent of ALS cases.
In 20 percent of cases, the fault is in the SOD1 gene, which codes for an antioxidant enzyme that protects cells from damage.
A smaller percentage goes to changes in TARDBP (4 percent) and FUS (5 percent).
Both of these genes code for key factors involved in making proteins in the cell.
Depending on the type of ALS, "the proportions in which the disease can be explained by genetic factors are only 8 to 60 percent," explains Eva Feldman, professor of neurology at the University of Michigan.
However, there is increasing evidence that repeated and prolonged exposure to potential triggers in the external environment can increase someone's risk of developing ALS, especially its sporadic form.
This led Feldman and her colleagues to investigate.
"We suspect the presence of something we call an ALS 'exposure,' a sum of exposures to a toxic environment that increase risk," Feldman says.
The team found that long-term exposure to organic chemical pollutants, metals, pesticides, microparticles in construction dust, and poor air quality all contribute to a person's risk of ALS.
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Neil Thakur, chief mission officer at the ALS Association, says there is no single cause and effect for ALS.
"It's always a combination of factors," he says.
"Even if you have a risk factor or genetic profile, it's not 100 percent certain you'll get ALS."
But there is some evidence that exposure to diesel particulate matter, jet fuel, microparticles from incinerators, pesticides and aerosols may increase the risk of developing ALS, he adds.
Military personnel, for example, are extremely exposed to these and appear to have an increased chance of contracting the disease, he says.
There is also evidence that the presence of lead in your drinking water, smoking and contact sports can trigger ALS.
However, there are still many unknowns.
Studies assessing the impact of lifetime alcohol and cigarette smoking before an ALS diagnosis show that being sober and a non-smoker does not necessarily protect you.
(These factors reduce a person's risk of developing various other conditions, of course—so there are plenty of other reasons to limit alcohol and smoking.)
One of the challenges facing scientists and doctors investigating the causes of ALS (and MND in general) is that they are fortunately rare diseases.
Within the small number of patients, not everyone is willing or able to participate in research.
And there are many differences in genetics and lifestyle that could affect the results.
Even if a genetic change is found in four percent of cases, for example, there may not be enough people in that group to see a clear difference between those who were exposed to certain chemical pollutants and those who were not.
"It takes a long time to fully recruit enough people for clinical testing in ALS, because the disease develops rapidly and people are suitable for testing only in the early stages of the disease," says Thakur.
"If you have ALS in your family and you have the ALS gene, you can explore whether you can participate in trials that would help you and others."
Feldman also says that her team's research looking at the combined risk of genetic and environmental factors is "challenging" because they suspect that multiple genes -- dozens or perhaps even hundreds -- contribute to the so-called "polygenic risk profile" of ALS.
This risk profile comes "in addition to the traditional risk from a single gene," she says.
The team is now investigating how this polygenic risk profile may interact with environmental factors to cause ALS.
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At this time, ALS cannot be cured.
But the Food and Drug Administration has approved several treatments that can help slow the rate of its progression and give people a little more time.
These drugs have a range of mechanisms, ranging from reducing the levels of certain chemicals around the brain and spinal cord to preventing nerve cell death.
It also seems possible that targeted treatments against the effects of a particular phallic gene might be useful.
A recent early trial of a drug aimed at reversing the damage done by the SOD1 mutation has led to some promising preliminary results, for example.
Knowing which genetic mutations may have been responsible for a person's diagnosis of ALS may not be particularly comforting to someone currently experiencing it.
The emphasis of the ALS Association is to provide support and guidance to people with the condition and their families.
"The strategy of the ALS Association is to live with the condition until we find a cure," says Thakur.
The organization advocates for high-quality care that includes health care professionals from a wide range of different fields, which can enable someone to live a more active life for several months longer, he says.
The association also plans to publish guidelines on how to reduce the risk of potential causes of developing ALS, he says.
The challenge, however, is funding appropriate research.
In addition to discovering how much each gene or environmental factor can influence, more studies are needed on how to apply the knowledge gained.
"The real question is not why do people get ALS, but what can we do to prevent or treat it," Thakur says.
Regardless of the cause, the progression of this progressive disease will continue.
Family and friends will have to respond to each new level of deterioration with love and patience, as Sandra Bulok did.
However, a better understanding of the scientific background behind this devastating condition will hopefully lead to more effective treatments and, one day, may even help prevent new cases from occurring.
And that always came in handy.
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