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Scientists discover urinary biomarker that may help track ALS

March 22, 2017

A study in Neurology suggests that analyzing levels of the protein p75ECD in urine samples from people with amyotrophic lateral sclerosis (ALS) may help monitor disease progression as well as determine the effectiveness of therapies. The study was supported by National Institute of Neurological Disorders and Stroke (NINDS) and National Center for Advancing Translational Sciences (NCATS), both part of the National Institutes of Health.

Mary-Louise Rogers, Ph.D., senior research fellow at Flinders University in Adelaide, Australia, and Michael Benatar, M.D., Ph.D, professor of neurology at the University of Miami, and their teams, discovered that levels of urinary p75 ECD increased gradually in patients with ALS as their disease progressed over a 2-year study period.

"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, Ph.D., program director at NINDS. "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."

Further analysis of the samples from 54 patients revealed that those who began the study with lower levels of urinary p75ECD survived longer than did patients who had higher levels of the protein initially, suggesting that it could be a prognostic marker of the disease and may inform patients about their illness. Dr. Benatar and his team noted that this may be useful in selecting participants for clinical trials and in improving study design.

The protein p75 is important early in life, but does not appear in adults unless motor neurons are injured. Previous studies in mouse models of ALS reported that p75 was re-expressed in motor neurons as the animals became sick and p75ECD was found in the urine of the mice even before they exhibited muscle weakness. p75 has also been seen on motor neurons in post-mortem tissue from ALS patients.

"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. Additionally, the ease of obtaining urine samples could help reduce the burden of patient participation in clinical studies," said Dr. Benatar.
-end-
This study was funded by the NIH's Clinical Research in ALS and Related Disorders for Therapeutic Development (CReATe) Consortium, which is part of the Rare Diseases Clinical Research Network, an initiative of the Office of Rare Diseases Research at NCATS. The goal of the consortium is to advance therapy development by improving the understanding of ALS and related neurodegenerative disorders.

ALS is a fatal neurodegenerative disease in which motor neurons, cells that control muscle activity such as walking, talking and breathing, gradually die off, resulting in paralysis. There is no cure for ALS.

"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," said Dr. Gubitz.

More research is needed to validate the use of urinary p75ECD as a biomarker of ALS and to further investigate the role of the protein in the disease.

This work was supported by the NINDS and NCATS (NS092091). More information about the study may be found on ClinicalTrials.gov, using the trial identifier NCT02327845.

References:

Shepheard SR et al. Urinary p75ECD: A prognostic, disease progression, and pharmacodynamics biomarker in ALS. Neurology. February 22, 2017. https://www.ncbi.nlm.nih.gov/pubmed/28228570

For more information:

https://www.ninds.nih.gov/Disorders/All-Disorders/Amyotrophic-Lateral-Sclerosis-ALS-Information-Page

https://www.rarediseasesnetwork.org/cms/create

The NINDS is the nation's leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIH/National Institute of Neurological Disorders and Stroke

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