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Scientists are beginning to see early results in their race to discover the causes of amyotrophic lateral sclerosis (ALS).
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- Author: Sarah Pitt
- Roll, BBC Future
9 hours ago
Three years ago, at the age of 54, he was unfortunately diagnosed with amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, named after the American baseball player who developed the disease in 1939.
In recent years, we have been able to follow several wellknown ALS victims, including young people who did not suffer from other health problems. However, the mystery surrounding the possible causes of amyotrophic lateral sclerosis remains unsolved.
But recent research has revealed some clues. Could we finally be on the way to unraveling the true causes of this devastating condition?
ALS is a form of motor neuron disease. It is a painful and debilitating condition that causes people to gradually lose their motor neurons the cells that control voluntary muscle movements. The result is that patients slowly lose control of their own bodies.
A recent analysis of available data estimates that the condition affects approximately five in 100,000 people in the United States.
The disease is more common in men and is diagnosed on average around age 60. But it can also affect significantly younger people.
Most people live only a few years after diagnosis, but there are notable exceptions. One of them was British physicist Stephen Hawking, who was diagnosed with a form of motor neuron disease at the age of 21 and died in 2018 at the age of 76.
The reasons why people develop ALS are complex. In 1015% of those affected, the cause is familial. In these cases, a mutation in a particular gene would have been passed down through generations.
It is not certain whether you will develop the disease if one of your parents or ancestors had ALS, but there may be stories in the affected family of a cousin or grandparent who also suffered from the devastating disease.
It turns out that when hereditary ALS develops, the gene affected is not always the same, even if the consequences are identical. And then there are the 8590% of people who develop the nonhereditary form of ALS for them it is even more difficult to determine the cause of the disease.
When a person is diagnosed with ALS and no one in the family says something like, “Your greatuncle had it,” the case is considered a onetime, random event, or “sporadic.”
Current research suggests that genetic mutations could be one of the causes. However, these are likely small changes in a few different genes, rather than the drastic and obvious biological errors that occur in familial ALS.
Changes in up to 40 genes have been identified that increase the risk of developing sporadic ALS, but the disease is extremely rare.
Complex genetics
The most common is the C9orf72 gene, which is related to the regulation of muscle and nerve cells. This genetic change occurs in 30% of ALS cases.
In 20% of cases, the error lies in the SOD1 gene, which codes for an antioxidant enzyme that protects cells from damage. And a smaller percentage corresponds to changes in the TARDBP (4%) and FUS (5%) genes. These two genes encode important factors that are involved in the production of proteins within the cell.
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Amyotrophic lateral sclerosis affects the nerve cells that control the voluntary movements of muscles called motor neurons
Nongenetic factors
Depending on the type of ALS, “the disease can only be explained by about 8 to 60% by genetic factors,” says neurology professor Eva Feldman from the University of Michigan in the US.
“We suspect the existence of the socalled ALS exposome, which is the sum of toxic environmental exposures that increase the risk [da doença]“ explains Feldman.
The director of the North American organization ALS Association, Neil Thakur, explains that there is no absolute causeandeffect relationship for ALS.
“It’s always a combination of factors,” he says. “Even if you have a risk factor or genetic profile, there is no 100% certainty that you have ALS.”
However, Thakur points out that there is evidence that exposure to particulate matter from diesel fuel, kerosene and campfires, as well as pesticides and aerosols, may increase the risk of developing ALS.
For example, he states that military personnel are highly exposed to these materials and appear to be at higher risk of contracting the disease.
There is also evidence that the presence of lead in drinking water, smoking and contact sports can trigger amyotrophic lateral sclerosis. However, many uncertainties remain.
One of the difficulties that doctors and scientists face in researching the causes of ALS (and motor neuron disease in general) is the fact that, fortunately, they are rare diseases.
Among the few patients, not all are willing or able to participate in research studies. And there are many genetic and lifestyle differences that can influence results.
For example, even if genetic changes are detected in 4% of cases, there may not be enough people in that group to see clear differences between those who were exposed to a particular chemical pollutant and those who were not.
“It takes a long time to recruit enough people for an ALS clinical trial because the disease progresses very quickly and patients can only participate in the early stages of the disease,” explains Thakur. “If you have ALS in your family and have an ALS gene, you can see if you can participate in studies that would help you and others.”
Feldman adds that studying the combined risk of genetic and environmental factors “represents a challenge” for his research team. They suspect that countless genes—dozens, perhaps even hundreds—contribute to what they call the “polygenic risk profile” of ALS.
In their opinion, this risk profile is “in addition to the traditional risk of isolated genes.” The team is now exploring how this polygenic risk profile may interact with environmental factors and cause ALS.
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There is currently no cure for ALS, but there are treatments that can slow the progression of the disease or help control symptoms.
Looking for good news
Amyotrophic lateral sclerosis is currently not curable. But the U.S. Food and Drug Administration (FDA) has approved several treatments that may help slow the progression of the disease and give people a little more time.
These drugs have a number of mechanisms. They can reduce the levels of certain substances in the brain and spinal cord and even prevent the death of nerve cells.
Apparently it may also make sense to use targeted treatments to combat the effects of a specific defective gene. For example, a recent initial trial of a drug to combat damage caused by the SOD1 mutation produced promising preliminary results.
But just knowing which genetic mutations might be responsible for diagnosing ALS in patients may not be of much comfort to people suffering from the disease. Therefore, the aim of the ALS Association is to offer support and advice to those affected and their families.
“The ALS Association’s strategy is to make life possible [com ELA] until we have a cure,” says Thakur.
According to its director, the organization is committed to providing quality care involving medical professionals from diverse backgrounds that can allow people to live more active lives for a few months longer. In addition, the association plans to publish guidelines to reduce the risks of possible factors contributing to the development of ALS.
The big challenge, however, is finding funding to carry out the necessary research.
In addition to determining what contribution each individual gene or environmental risk factor may have, further studies are needed to find a way to apply the knowledge ultimately acquired.
“The real question is not why people suffer from ALS, but what we can do to prevent or treat it,” emphasizes Thakur.
Regardless of the causes, the advance of this progressive disease will continue. Relatives and friends must respond with love and patience to any degree of deterioration in their loved one, as Sandra Bullock did.
But a better understanding of the science behind this devastating disease could one day lead to more effective treatments and, who knows, even help prevent new cases from occurring.
And such good news is always welcome.