Protein Test Predicts Progression in Lou Gehrig's Disease

The test measures the phosphorylated neurofilament heavy subunit (pNF-H), a promising putative biomarker in ALS, in blood and cerebrospinal fluid (CSF). These are proteins that provide structure to motor neurons, and when these nerves are damaged by the disease, the proteins break down and float free in blood serum and in the spinal fluid.

Scientists from the Mayo Clinic (Jacksonville FL, USA) measured pNF-H concentration by monoclonal sandwich enzyme-linked immunosorbent assay (ELISA) in 43 plasma and serum and 20 CSF samples in ALS patients collected at the Mayo Clinic and Emory University (Atlanta, GA, USA). In the Mayo 12 month follow-up cohort, median pNF-H level was 4.38 ng/mL in CSF, 0.66 ng/mL in serum and 0.91 ng/mL in plasma. Plasma and serum pNF-H levels were highly correlated and also correlated, but to a lesser degree, in CSF and plasma and in CSF and serum.

In individual patients, examination of plasma or serum pNF-H levels in relation to survival from date of sample collection suggested an association between increased pNF-H concentration and the survival endpoint in the Mayo 12 month follow-up cohort. A doubling in pNF-H in plasma was associated with nearly a twofold increase in the risk of a death endpoint and a doubling of pNF-H in serum was associated with a greater than twofold estimated increase in the risk of death endpoint.

Kevin Boylan, MD, the senior author of the study said, "Many ALS scientists have been trying to develop a molecular biomarker test for nerve damage like this, and we are encouraged that this test shows such promise. Because blood samples are more readily collected than spinal fluid, we are especially interested in further evaluating this test in peripheral blood in comparison to spinal fluid. We demonstrated a solid association between higher levels of this protein and a faster progression of muscle weakness. There was also evidence suggesting that ALS patients with higher protein levels may have shorter survival.” The study was published on October 31, 2012, in the Journal of Neurology, Neurosurgery & Psychiatry.

Related Links:
Mayo Clinic
Emory University