In a significant breakthrough, scientists are closing in on uncovering the root cause of Lou Gehrig’s disease, an advancement that could also illuminate other debilitating motor neuron disorders.

Lou Gehrig’s disease, medically known as amyotrophic lateral sclerosis (ALS), impacts around 30,000 individuals in the United States. Those afflicted gradually lose the ability to control their muscles, which affects their ability to walk, talk, swallow, and ultimately breathe.

The precise cause of ALS remains elusive, particularly since the condition often arises spontaneously and without any familial history. Previous research has pointed towards the possibility of mutated genes or a complex interplay between genetics and environmental factors as potential causes.

In a recent study conducted by scientists at St. Jude Children’s Research Hospital in Tennessee, the genetics of 600 patients with various motor neuron disorders, including ALS, were meticulously analyzed.

The research revealed a notable discovery: 423 ultrarare genetic variants were common among many ALS patients and individuals suffering from hereditary spastic paraplegia (HSP). HSP is another motor neuron disease affecting 10,000 to 20,000 people in the US, characterized by muscle weakness due to its genetic inheritance.

Dr. Gang Wu, the statistician leading the study, emphasized that rare genetic variants in patients with motor neuron conditions have frequently been overlooked in research, signifying a potential area for further investigation and understanding.

He added, however: ‘But by analyzing a large dataset with multiple related motor neuron disorders, we found that genes associated with HSP could also increase the risk for sporadic ALS.’

The study could pave the way for scientists to better understand the causes of ALS, who is at risk for the disease and potentially lead to the development of new treatments.

Famed physicist Stephen Hawking was diagnosed with amyotrophic lateral sclerosis (ALS) (shown above in 2016)

Study co-author Dr J. Paul Taylor, the vice president of St Jude’s, added: ‘Extensive progress has been made over the past decade to decode the genetic landscape of motor neuron diseases such as ALS and HSP.

‘This study furthers that cause by showing the overlapping contributions of… distinct genes, offering a clear path forward to more accurate diagnosis and care.’

ALS tends to be diagnosed between the ages of 55 and 75 years, with symptoms becoming progressively worse.

There is no cure for the disease, but doctors try to treat patients by prescribing drugs to reduce pain and slow its progression. 

Patients live for an average of two to five years after their diagnosis. 

Both ALS and HSP occur because motor neurons, which control voluntary movement, begin to break down and die, causing muscle weakness that leaves patients struggling with day-to-day tasks like walking, cooking and cleaning.

But the two conditions progress differently. In ALS, the muscle weakness may begin in the arms, legs, head or neck, whereas in HSP, the weakness begins in the legs.

Previous studies have suggested that separate genetic variants trigger the conditions. In patients suffering from HSP, nearly all cases are linked to variants passed down from parent to child, whereas in ALS, only about 10 percent of cases are.

Eric Dane, an actor, has also said that he has been diagnosed with ALS. He is best known for his heartthrob role as Dr Mark Sloan, also known as McSteamy, on Grey’s Anatomy

In their new study, published in Translational Neurodegeneration, researchers analyzed genetic data from patients with ALS, HSP and two other motor neuron diseases, progressive muscular atrophy (PMA) and primary lateral sclerosis (PLS).

PMA is a condition where nerve cells in the spinal cord slowly degenerate, leading to problems with movement and muscle wasting, while PLS is a condition where nerve cells in the brain that control movement start to deteriorate, causing similar symptoms.

About 10,000 to 25,000 children and adults in the US have PMA, according to the American Brain Foundation, while 300 to 500 people in the country have PLS, according to the Spastic Paraplegia Foundation.

In the study, a total of 472 patients had ALS and 162 patients had HSP, equivalent to 90 percent of all participants.

Another 20 patients included in the study had PMA and 47 had PLS.

Overall, scientists found there were 423 overlapping genetic variants in 222 patients suffering from ALS and 134 patients suffering from HSP.

Among these, 100 genetic variants in 124 patients were suggested to be pathogenic, meaning they could potentially be the cause of the disease.

Overall, the researchers said they found ‘significant overlap’ in ultrarare genetic variants between patients with ALS and HSP.

Shown above is a neuron, with these cells being affected by motor neuron disease (stock image)

The researchers split patients into two groups; familial, or those who had a family history of their condition, and non-familial, or those who did not have a family history of their condition.

They said in patients with non-familial ALS, many shared similar genes to those diagnosed with HSP.

Dr Michael Benatar, a neurologist at the University of Miami who was also involved in the research, said: ‘One of the foundational principles underlying [our research]… was the idea that we should study multiple disorders, with the expectation that we could leverage knowledge from one, to understand another.

‘The work published today underscores the value of this approach.’