Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that leads to the death of nerve cells that control movement. As the disease progresses, people gradually lose the ability to move and eventually to breathe. ALS is fatal and, so far, incurable. However, new findings may offer hope for future therapies.

 

ALS, also known as Lou Gehrig’s disease, affects approximately 30,000 people in the United States alone. Despite ongoing research, its causes remain largely unknown. Currently, there is no cure, and only a few treatments are available to improve quality of life or slightly prolong life expectancy.

 

This condition is sometimes characterized by “focal onset,” meaning that symptoms appear one by one in a specific area of the body, such as an arm, before spreading to other areas. As motor neurons in the spinal cord and brain begin to die, a person with ALS may first experience paralysis in one limb, then another, and so on until the motor cells responsible for breathing muscles are affected, leaving the person unable to breathe.

 

At present, no single test can provide a definitive diagnosis of ALS. According to the National Institute of Neurological Disorders and Stroke, doctors typically diagnose the condition based on symptoms. For this reason, many people receive an ALS diagnosis only after the disease has already progressed significantly.

 

New research from the University of Illinois at Chicago has identified, for the first time, a set of biomarkers that distinguish people with ALS from those without a neurodegenerative disease. These findings, reported in the journal Neurobiology of Disease, could help doctors diagnose ALS earlier and may open new avenues for targeted therapies.

 

In the new study, researchers reanalyzed samples of motor neurons and associated cells collected from the spinal cords of individuals who had died from ALS, as well as samples from healthy individuals without neurodegenerative disease.

 

The researchers had previously examined these samples in 2010, comparing cell populations by analyzing gene expression within each cell. At the time, they collected samples from regions of the spinal cord that appeared to be less affected in people with ALS.

 

“Since there must be cellular changes occurring in spinal cord regions adjacent to areas where the disease has clearly affected motor neurons in the spine, we wanted to look at neurons from these adjacent areas to determine if they are different from healthy tissue,” explains lead researcher Dr. Fei Song.

 

“The debilitating disease has no effective treatment to stop disease progression, and there are only two medications that can prolong patient survival by a few months. So new drug targets, especially ones that could be given in the earlier stages of the disease, are very much needed,” she adds.

 

The team had already identified some notable differences between the neurons and other cells found in the spinal cords of people with ALS compared with those in healthy individuals.

 

In the current study, the scientists decided to reevaluate those samples using a new bioinformatics analysis method to reassess the genetic data they had initially collected. This allowed the team to identify specific types of cells within the samples more precisely.

 

Through this analysis, the researchers discovered that individuals who had died from focal-onset ALS had different types of motor neurons compared with healthy individuals.

 

Furthermore, these differences were linked to microglia and astrocytes, two specialized types of neural cells. These cells were not present in samples taken from the same spinal cord regions in healthy participants.

 

“When we examined the data, it was clear that the mixture of cells from the ALS patients was very different from patients with no neurodegenerative disease,” notes Dr. Song.

 

The researchers believe that these findings could eventually help scientists better understand the biological mechanisms behind ALS. In the future, this knowledge may support the development of more targeted and effective therapeutic strategies for the disease.