ALS Biomarker Discovered in Urine


Increased levels of a specific protein was associated with progression of amyotrophic lateral sclerosis.

Findings from a study published by Neurology suggest that a novel biomarker may be able to monitor disease progression in patients with amyotrophic lateral sclerosis (ALS). The levels of the p75ECD protein found in urine samples may also be able to determine the efficacy of certain treatments.

ALS is a neurodegenerative disease in which motor neurons gradually die off, resulting in paralysis. Currently, there is no cure for ALS, so discovering a potential biomarker that may track progression is a significant development.

In the 2-year study, the authors found that levels of urinary p75ECD increased along with disease progression. This finding indicates that the protein could be a non-invasive way to determine ALS progression.

“It was encouraging to see changes in p75ECD over the course of the study, because it suggests an objective new method for tracking the progression of this aggressive disease,” said Amelie Gubitz, PhD, program director at the National Institute of Neurologic Disorders and Stroke. “In addition, it indicates the possibility of assessing whether levels of that protein decrease while patients try future treatments, to tell us whether the therapies are having any beneficial effects.”

An additional analysis of samples from 54 patients demonstrated that those with lower baseline levels of p75ECD had longer survival than those with high levels at baseline, according to the study. Levels of p75ECD may be used as a biomarker for ALS, and could even help patients better understand their condition.

The study authors also indicated that p75ECD could also be used as a way to determine which patients should be included in clinical trials.

The protein is important in early life, but only appears in adults when motor neurons are injured. Mouse studies of ALS have shown that p75ECD was expressed in motor neurons as the animals progressed, and the protein was discovered in the urine even prior to muscle weakness.

In post-mortem tissue from patients with ALS, investigators have also discovered p75ECD on motor neurons.

“As we move potential new therapies into phase-2 clinical trials, our findings suggest that p75ECD may tell us a lot about how well the treatments are working,” said researcher Michael Benatar, MD, PhD. “Additionally, the ease of obtaining urine samples could help reduce the burden of patient participation in clinical studies.”

This study was funded by the National Institutes of Health’s Clinical Research in ALS and Related Disorders for Therapeutic Development Consortium. The goal of the consortium is to improve the understanding of ALS and related diseases.

“The consortium provides a foundation for ALS research to help move the field forward by advancing our knowledge of the progression of this disease as well as identifying potential causes,” Dr Gubitz concluded.

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