Researchers discovered that levels of a protein in urine gradually increased in patients with ALS as their disease progressed over 2 years.
These results suggest a potential biomarker to monitor disease progress and the effectiveness of therapies.
The ability to better track the progress of ALS would enable doctors to adjust treatments and test novel therapies.Comstock Images/Stockbyte/Thinkstock
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease in which motor neurons—the brain and spinal cord cells that control muscle activity—gradually die off. As motor neurons degenerate or die, they stop sending signals to muscles. Unable to function, the muscles weaken and waste away. This can affect a person’s ability to chew, walk, breathe, and talk. ALS is progressive, meaning the symptoms get worse over time. Currently, there’s no cure and no effective treatment to halt progress of the disease.
A protein in motor neurons called p75 is important in early life, but doesn’t appear in adults unless motor neurons are injured. Previous studies in mouse models of ALS found that p75 was re-expressed in motor neurons as the animals became sick. The part of p75 that sticks out from the cells—its extracellular domain (p75ECD)—was found in the urine of the mice even before they exhibited muscle weakness.
To investigate whether p75ECD could be used as a biomarker to monitor ALS disease progression in people, a team led by Dr. Mary-Louise Rogers at Flinders University and Dr. Michael Benatar at the University of Miami analyzed urine samples from patients with ALS over a 2-year period. The study was supported by NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and National Center for Advancing Translational Sciences (NCATS). Results were published in Neurology on March 21, 2017.
The team analyzed urine samples from 54 patients with ALS and 45 healthy controls. On the first study visit, p75ECD levels were higher in patients with ALS than controls. Levels of the protein increased gradually in patients with ALS as their disease progressed over the 2-year study period. Study participants who began the study with lower levels of urinary p75ECD survived longer than patients who had higher levels of the protein (13.9 months versus 8.9 months).
“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,” says Dr. Amelie Gubitz, a 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.”
More research is needed to validate the use of urinary p75ECD as a biomarker of ALS and to further investigate the role of p75 in the disease.
Funding: NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and National Center for Advancing Translational Sciences (NCATS); Motor Neurone Disease Research Institute of Australia; Flinders University Centre for Neuroscience; FMC Foundation; Muscular Dystrophy Association; ALS Recovery Fund; and Australian Rotary Health.
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