Biomarker for ALS progression shows promise

Levels of a neurofilament subunit in cerebral spinal fluid (CSF), serum, or plasma may predict disease progression in individuals with amyotrophic lateral sclerosis (ALS), report researchers.

The condition, which is the most common of the motor neuron diseases, is fatal to the majority of patients within 3 years of diagnosis.

"Many ALS researchers have been trying to develop a molecular biomarker test for nerve damage like this, and we are encouraged that this test shows such promise," said lead author Kevin Boylan (Mayo Clinic, Jacksonville, Florida, USA) in a press statement.

As reported in the Journal of Neurology, Neurosurgery & Psychiatry, Boylan and co-researchers evaluated the association between the phosphorylated neurofilament heavy subunit (pNF-H) and disease progression among patients using the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R).

"To our knowledge, this is the first report examining pNF-H in peripheral blood in relation to a validated ALS functional outcome measure," says the team.

Levels of pNF-H in CSF have previously been shown to correlate with rate of disease progression and survival in individuals with ALS. However, due to the difficulty in obtaining CSF as opposed to peripheral blood, Boylan et al decided to see if levels in plasma and serum also predicted outcomes.

The study included three cohorts of patients, including one in which 20 patients were followed up at 4 and 12 months (12-month group), one with 20 patients followed up for 4 months only (4-month group), and one with 23 patients for whom survival data but not serial ALSFRS-R data were available.

In the 12-month cohort, higher CSF pNF-H levels correlated with a faster decline from baseline in ALSFRS-R at both 4 months and 12 months. A similar significant relationship between higher serum pNF-H levels and faster decline in ALSFRS-R was observed at 4 months, but this was not significant at 12 months, while the association of plasma pNF-H levels with decline was not significant at either 4 or 12 months. However, when the 4-month cohort was included in the analysis, the association between a higher plasma pNF-H level and more rapid decline was significant.

Further analysis of the 12-month group showed that a doubling in pNF-H in plasma or serum levels at the time of sample collection (or baseline) was associated with an approximate twofold increase in risk for death at the end of follow up, at hazard ratios of 1.87 and 2.10, respectively. A similar association between plasma pNF-H and shorter survival was observed in the 4-month group and in all three cohorts combined.

However, elevated CSF pNF-H was not associated with shorter survival from the date of sample collection. "The small sample size and resulting high variability may account for this, but the data also leave open the possibility that factors governing day-to-day pNF-H concentration in CSF, and potentially its detection by our assay, may differ from those in serum or plasma."

"Further study of pNF-H in larger numbers of patients, particularly examination of serially collected longitudinal samples of plasma, serum, and CSF obtained in parallel, would help to address this question, as would further refinement of our pNF-H assay."

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