7:55 PM
 | 
Dec 06, 2018
 |  BC Innovations  |  Tools & Techniques

Filaments line up as MS biomarker

Why neurofilaments could become the go-to biomarker for neurodegeneration

Neurofilament assays appear on track to become the biomarker of choice for a wide range of neurodegeneration studies, given their tight correlation with axon damage and detectability in blood.

If prospective trials can reinforce the positive data from retrospective clinical studies, the biomarker could see wide uptake in multiple sclerosis and beyond.

As researchers search for biomarkers to supersede the symptom-based diagnostics and clinical trial endpoints that limit progress in neurology, blood-based readouts rise to the top of the wish list because they are less invasive than obtaining CSF via spinal taps, and cheaper than imaging.

Academic and industry researchers are ramping up activity on neurofilaments as a biomarker, because their linkage with axon degeneration would find use in multiple sclerosis, Alzheimer’s disease and a host of other neurodegenerative indications.

“This is the first biomarker showing robust correlation with neuronal injury in blood and it works across diseases,” Henrik Zetterberg, an academic expert on AD biomarkers, told BioCentury. Zetterberg is a professor and chief physician at the University of Gothenburg and professor of neurochemistry at University College London.

In February, FDA released guidance stating it is open to a biomarker-based endpoint for trials of early stage AD when symptoms aren’t yet present, although it did not name a specific biomarker.

In April, NIH’s National Institute on Aging (NIA) and the Alzheimer’s Association released a framework advocating for a biological definition of the disease and recommending a composite biomarker dubbed the “ATN system” that involves β-amyloid deposition, tau aggregation and neurodegeneration (see “New Framework Advocates Biomarker-Based Definition of AD”).

“This is the first biomarker showing robust correlation with neuronal injury in blood and it works across diseases.”

Henrik Zetterberg, University of Gothenburg

“People now recognize the neurofilament light chain assay in blood as the ‘N’ in that acronym,” said Zetterberg.

After decades of only being able to detect neurofilaments in CSF, Quanterix Corp. has emerged as the major provider of blood-based neurofilament assays, using its ultra-sensitive, ELISA-like Simoa platform.

At least four biopharma companies are using the system, with the MS field leading the charge via retrospective studies on blood samples from previous clinical trials. The goal is to replace expensive MRIs as a measurement of disease activity, said Bernd Kieseier, a medical director at Biogen Inc.

“We are literally measuring every serum sample from past trials -- placebo and drug-treated,” said Kieseier.

He said Biogen is continuing to plan retrospective studies, and will then discuss a regulatory path with FDA.

Novartis AG has studied the biomarker in post hoc studies of its MS drug Gilenya fingolimod. But Dan Bar-Zohar, global head of neuroscience development, noted that retrospective studies will only get it so far.

“The FDA wants prospective, not post hoc, data and we are lucky enough that we have ongoing pivotal studies that include the assays,” said Bar-Zohar.

Sensitivity breakthrough

Neurofilaments have been on the radar in neurodegeneration for two decades...

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