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ALS Association-Funded Study Finds Blood Protein May Serve as Biomarker to Measure ALS Decline

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According to a new study published online on October 31 in the Journal of Neurology, Neurosurgery and Psychiatry, a protein in the blood may serve as a biomarker, providing amyotrophic lateral sclerosis (ALS) researchers a way to track the progress of the disease and potentially to determine quickly whether a patient is responding to therapy. The study was supported by the EMD/ALS Biomarker Research Fund through the Keith Worthington Chapter of The ALS Association and is one of 80 active projects in The ALS Association’s Translational Research Advancing Therapies (TREAT ALS™) research portfolio.

ALS is a progressive neurodegenerative disease that affects nerve cells in the brain and the spinal cord. Eventually, people with ALS lose the ability to initiate and control muscle movement, which often leads to total paralysis and death within two to five years of diagnosis. For unknown reasons, veterans are twice as likely to develop ALS as the general population. There is no cure and only one drug approved by the U.S. Food and Drug Administration (FDA) that modestly extends survival.

This new study showed that elevated blood levels of a protein called phosphorylated neurofilament heavy subunit (pNF-H) correlated with more rapid decline in patients with ALS. Higher levels of pNF-H were also associated with a greater risk of death during a twelve-month period.

“This finding is very exciting for the ALS community,” commented Lucie Bruijn, Ph.D., Chief Scientist for the ALS Association. “Although a biomarker is only proven once tested in a clinical trial and shown to be more predictive than the currently available measure of progression in ALS, this protein appears to be a very promising biomarker of disease progression in a relatively large group of patients and should allow us to conduct shorter clinical trials and speed the search for new therapies.” A biomarker is a substance or characteristic that changes with the disease state. Blood cholesterol level is a biomarker for heart disease risk, for example.

In the study, researchers at the Mayo Clinic in Jacksonville, Florida, and Emory University in Atlanta, Georgia, measured the concentration of pNF-H in the blood and in the cerebrospinal fluid (CSF) of ALS patients throughout the course of a year. They found that those patients who began with higher levels of the protein in either blood or CSF tended to progress faster than those with lower levels. In addition, those with higher levels were at greater risk for dying during the course of the study than those with lower levels.

Previous studies of potential ALS biomarkers have mainly examined proteins in the CSF, whereas in this study, both CSF and blood levels of pNF-H were measured. Obtaining a blood sample is much safer and easier than obtaining a CSF sample and therefore a reliable blood marker would be advantageous.

“If pNF-H proves to be a reliable biomarker,” Dr. Bruijn continued, “it may provide ALS researchers with a more objective way to track disease progress than the functional rating scale that is currently used in clinical trials.”

This scale measures many aspects of patient function (such as difficulty walking or breathing) that may fluctuate from day to day. “Clinical trials of therapies that aim to slow the disease course could be shorter if researchers had a way to more accurately measure response to therapy,” Dr. Bruijn noted.

Study: Phosphorylated neurofilament heavy subunit (pNF-H) in peripheral blood and CSF as a potential prognostic biomarker in amyotrophic lateral sclerosis

Source: ALS Association