Breakthrough Discovery on ALS Causes Opens Path to New Treatments

Scientists at St. Jude’s Children’s Research Hospital in Tennessee have made significant strides in understanding the causes of amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig’s disease. Their research suggests that overlapping genetic factors may contribute to ALS and other motor neuron diseases, paving the way for potential new treatments.

ALS affects approximately 30,000 people in the United States, leading to a gradual loss of muscle control that impacts daily activities such as walking, talking, and swallowing. Despite its devastating effects, the exact cause of ALS remains elusive. Previous theories have pointed to genetic mutations or complex interactions between genetics and environmental factors as possible triggers.

In their recent study, researchers analyzed the genetic data of 600 patients with various motor neuron conditions, including ALS and hereditary spastic paraplegia (HSP). This genetic analysis revealed 423 ultrarare genetic variants shared between ALS patients and those suffering from HSP, a hereditary condition affecting 10,000 to 20,000 people in the U.S. that also leads to muscle weakness.

Dr. Gang Wu, a statistician and lead author of the study, emphasized that rare genetic variants are often overlooked in research. He stated, “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.” This discovery may enhance the understanding of who is at risk for ALS and facilitate the development of targeted treatments.

The study’s co-author, Dr. J. Paul Taylor, vice president of St. Jude’s, noted the progress made in recent years to decode the genetic landscape of motor neuron diseases. He remarked, “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 typically presents between the ages of 55 and 75, with symptoms that worsen progressively. Unfortunately, there is no cure for the disease currently, and available treatments focus on alleviating pain and slowing progression. Patients diagnosed with ALS can expect an average lifespan of two to five years post-diagnosis.

Both ALS and HSP result from the degeneration of motor neurons, which are responsible for voluntary movement, but they progress differently. In ALS, muscle weakness may initiate in the arms, legs, head, or neck, while in HSP, symptoms typically begin in the legs. Previous studies indicated that distinct genetic variants trigger these conditions, with nearly all HSP cases linked to inherited variants, whereas only about 10 percent of ALS cases are familial.

In their research, published in the journal Translational Neurodegeneration, scientists evaluated genetic information from patients with ALS, HSP, and two additional motor neuron diseases: progressive muscular atrophy (PMA) and primary lateral sclerosis (PLS). PMA affects approximately 10,000 to 25,000 children and adults in the U.S., while PLS has around 300 to 500 cases reported.

Of the participants in the study, 472 patients had ALS and 162 patients had HSP, accounting for about 90 percent of the total sample. The findings revealed that among the genetic variants identified, 100 variants in 124 patients were deemed pathogenic, potentially contributing to the onset of these diseases.

The researchers divided patients into two categories: familial, for those with a family history of the condition, and non-familial, for those without. Their analysis demonstrated that many non-familial ALS patients shared similar genes with HSP patients, highlighting a significant connection.

Dr. Michael Benatar, a neurologist at the University of Miami and a contributor to the research, emphasized the value of studying multiple disorders simultaneously. “The work published today underscores the value of this approach,” he said, reinforcing the importance of collaborative research in advancing the understanding of complex neurological conditions.

As research continues, these findings may lead to improved diagnostic methods and treatment options for ALS and related motor neuron diseases, offering hope to patients and families affected by these challenging conditions.