In a major leap forward for neuroscience, researchers have uncovered key genetic clues behind amyotrophic lateral sclerosis (ALS) also known as Lou Gehrig’s disease and several other debilitating motor neuron conditions. The discovery, published in Translational Neurodegeneration, marks one of the most significant advances yet in understanding the biological roots of these diseases and brings renewed optimism for future cures.

ALS affects roughly 30,000 Americans, gradually robbing individuals of their ability to move, speak, swallow, and breathe. While about 10 percent of cases are inherited, most occur spontaneously, leaving scientists puzzled for decades. Famed physicist Stephen Hawking and actor Eric Dane are among the most recognized figures diagnosed with ALS.

Led by statistician Dr. Gang Wu at St. Jude Children’s Research Hospital in Tennessee, the study analyzed the genetic data of more than 600 patients suffering from four motor neuron diseases, including ALS, hereditary spastic paraplegia (HSP), progressive muscular atrophy (PMA), and primary lateral sclerosis (PLS). Researchers identified 423 ultrarare genetic variants, with about 100 classified as potentially disease-causing.

Dr. Wu noted that rare genes in motor neuron disorders are often overlooked. However, by comparing data across multiple related conditions, the team discovered that genes previously linked to HSP may also contribute to sporadic ALS, revealing a deeper genetic overlap than previously thought.

HSP, an inherited disorder that affects between 10,000 and 20,000 Americans, primarily causes muscle weakness in the legs. ALS, on the other hand, typically begins with weakness in the arms, legs, or facial muscles before advancing to respiratory failure. Despite their differences, both diseases stem from the progressive death of motor neurons — the nerve cells responsible for voluntary movement.

The study’s co-author, Dr. J. Paul Taylor, vice president of St. Jude’s, said the research provides “a clear path forward to more accurate diagnosis and care,” emphasizing how overlapping genes between ALS and HSP could refine treatment approaches.

Neurologist Dr. Michael Benatar of the University of Miami, another collaborator, underscored the study’s broader scientific value: “We should study multiple disorders with the expectation that we could leverage knowledge from one to understand another.”

The findings are expected to accelerate the development of early diagnostic tools, identify individuals genetically at risk, and guide future therapies targeting shared genetic mechanisms. With most ALS patients diagnosed between ages 55 and 75 and an average survival time of just two to five years, these insights could mark a turning point in the decades-long battle against motor neuron diseases.