Cerebrospinal Fluid Biomarker May Inform ALS Diagnosis, Treatment
A newly discovered potential biomarker may aid in the diagnosis and treatment of sporadic amyotrophic lateral sclerosis (ALS), according to a research letter published online ahead of print in the Journal of Neurology, Neurosurgery, and Psychiatry.
In sporadic ALS, which affects 90% of patients with the disease, motor neuron death is caused by dysregulation of RNA editing due to the downregulation of the RNA editing enzyme, the research team explained. The glutamine/arginine (Q/R) site of GluA2 messenger RNA (mRNA) is edited in healthy motor neurons and codes for the protein that forms a type of glutamate receptor called the AMPA receptor. In sporadic ALS, however, unedited Q/R site GluA2 mRNA results in motor neuron death.
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In the letter, researchers reported the identification of significantly reduced editing efficiencies at the Q/R site of GluA2 mRNA in the cerebrospinal fluid of patients with sporadic ALS compared with control subjects.
“In particular, patients with ALS with reduced editing efficiency experienced longer disease duration and advanced symptoms, particularly in the functioning of the lower limbs,” wrote corresponding author Shin Kwak, MD, PhD, a professor in the neurology department at Tokyo Medical University in Japan, and coauthors.
The authors noted that dysregulation of RNA editing is a current target in ALS therapy development.
“[I]t is believed,” they wrote, “that the editing efficiency at the Q/R site of GluA2 mRNA could be a biomarker not only for ALS diagnosis but also for determining treatable ALS cases.”
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