Could ALS biomarkers provide potential new drug targets?

Unique biomarkers for amyotrophic lateral sclerosis (ALS) have been discovered by researchers from the University of Illinois (IL, USA), that may offer potential new drug targets for the neurodegenerative disease. Currently, a lack of known biomarkers prevents early diagnosis of ALS – which manifests in paralysis due to the death of neurons controlling voluntary muscles – however, scientist believe cellular changes within spinal neurons may occur before symptoms are detectable.

“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,” explained Fei Song (UIC College of Medicine; IL, USA).

“The debilitating disease has no effective treatment to stop the 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.”

Motor neurons were collected from less affected regions of the spinal cord, in patients who died of ALS, where the tissue was assumed to be in the earlier stages of disease. A novel bioinformatics approach was then used to analyze of the genetic data, and this was compared with control samples from patients without the neurological disease.

Results of the study, reported in the journal Neurobiology of Disease, indicated that patients with focal-onset ALS presented different types of neurons in areas of the spinal cord less affected by the disease compared with patients without neurological disorders. Additionally, spinal neurons in patients who died of ALS were discovered to be associated with microglia and astrocyte cells, which were absent in the control samples.

“We found a novel and unique subtype of motor neurons in these patients never before reported,” commented Song. “Now that we have identified new subtypes of motor neurons and microglia present in ALS patients, we can begin to further study their roles in contributing to disease progression.”

Sources: Dachet F, Liu J, Ravits J & Song F. Predicting disease specific spinal motor neurons and glia in sporadic ALS. Neurobiol. Dis. 130(104523) (2019), https://today.uic.edu/researchers-describe-new-als-biomarkers-potential-new-drug-targets