NeuroVoices: Brett Morrison, MD, PhD, on Current and Future Biomarker Landscape in Peripheral Nerve Disease

Biomarker development in peripheral nerve disease has accelerated meaningfully in recent years, with neurofilament light chain emerging as the most broadly used tool across clinical trials and, increasingly, everyday practice. But as the field grows, so does the recognition that no single biomarker tells the whole story, and that different diseases may require very different measurement strategies. These were among the themes explored at the 2026 Peripheral Nerve Society (PNS) Annual Meeting, held June 13 to 16 in Maastricht, Netherlands.

Brett Morrison, MD, PhD, associate professor at Johns Hopkins University and program director of the neuromuscular fellowship, presented a talk during Education Day on current and future biomarkers for peripheral nerve diseases. His overview spanned the full landscape, from established tools like neurofilament light chain to emerging modalities including muscle MRI, targeted cytokine and complement markers in inflammatory neuropathy, and microRNA in diabetic peripheral neuropathy.

In this iteration of NeuroVoices, Morrison breaks down the different classes of biomarkers he covered, discusses the strengths and limitations of neurofilament light chain in peripheral nerve disease, highlights which emerging biomarkers are gaining traction, and shares his outlook on how biomarkers could reshape peripheral nerve clinical trial design over the next five years.

NeurologyLive: For our clinical audience who may not have had a chance to sit in on your presentation, give a brief overview of what you covered and why this topic was of interest to you.

Brett Morrison, MD, PhD: My talk was part of Education Day, and because of that I wanted to keep things very basic, very general, and pretty broad rather than focusing on my individual research. I started from the very basics, in terms of what a biomarker actually is, and then moved into the different uses of biomarkers, including diagnosis, monitoring, pharmacodynamic markers, and predictive markers.

From there I talked about the different types of biomarkers. When many of us think about biomarkers, we tend to think of blood tests or cerebrospinal fluid tests, but biomarkers are much broader than that. I spent a lot of time on blood-based tests, because there is a lot of biomarker development in that space, but I also covered clinical scales, electrophysiology, and imaging studies, which are increasingly being used as biomarkers as well.

Can you give our clinical audience a breakdown of some of the current and emerging biomarkers you touched on, and why you highlighted those specifically?

The one I highlighted most was neurofilament light chain, by far the most broadly used biomarker currently in peripheral nerve disease, and for several reasons. It is relatively inexpensive, it can be measured from a blood sample, and it is now available through major commercial laboratories, so clinicians can actually order it as a clinical test without needing access to a specialized research lab.

I spent time discussing its uses in terms of prognosis and monitoring, including in Guillain-Barre syndrome and CIDP, where it has been shown to correlate with disease progression. In GBS, for instance, neurofilament levels can reflect the degree of axonal injury and have shown some predictive value for future disability.

That said, I also touched on some of the important limitations. The biggest is that neurofilament light chain is non-specific. It is elevated not only in peripheral nerve diseases but in many central nervous system and neurodegenerative diseases as well. It also rises with age, renal disease, cardiac disease, and other conditions, so there are many situations where you would not necessarily expect elevation but see it anyway.

I think it is most useful when you are following an individual's level over time rather than relying on absolute values. In CIDP, for example, it can serve as one additional tool alongside clinical scales, physical exam findings, and disability scores like the iRODS or Inflammatory Neuropathy Cause and Treatment score to help assess whether a patient is still responding to treatment and whether adjustments are needed.

NfL clearly dominates the conversation right now, but what are some of the secondary or emerging biomarkers that may not get as much attention yet?

Muscle MRI is one I highlighted, and it has become a significant story particularly in the inherited neuropathy and CMT field. The challenge there is that many forms of CMT are very slowly progressive, so clinical scales often fail to detect meaningful change within a timeframe that is feasible for a clinical trial.

What researchers have found is that MRI can detect changes in fat fraction in distal muscles, essentially the earliest signs of denervation as muscle tissue converts to fibroadipose tissue, and these changes can be detected within a year. That makes it a much more practical endpoint for trials where waiting a decade for clinical change is not an option.

For inflammatory neuropathies, I also discussed the idea of measuring specific cytokines or complement levels that correspond to whatever immune pathway a given drug is targeting, rather than relying on broad global markers. And for conditions like diabetic peripheral neuropathy and chemotherapy-induced neuropathy, there has been meaningful research into microRNA changes.

MicroRNAs are small RNA molecules that can alter the transcription of dozens of genes simultaneously and have been found to be impacted in a variety of neuropathies. Some appear compensatory, while others may be more directly involved in pathogenesis. The limitation is that unlike neurofilament, microRNAs cannot be sent to a commercial lab, so they remain squarely in the research domain for now.

What does the outlook look like for integrating more biomarkers into peripheral nerve clinical trials over the next five years? Could we see neurofilament become a more standard secondary endpoint, and could some of these emerging markers make their way in as well?

Neurofilament is already there to a meaningful degree. I am involved in a number of clinical trials at Johns Hopkins, both in CIDP and in chemotherapy-induced neuropathy, and in several of those trials neurofilament has been incorporated as a secondary endpoint. It seems to correlate with disease severity well enough that investigators want to use it to help validate their primary endpoints.

For muscle MRI, the hope is that it will be incorporated into upcoming CMT trials. There has been a long-anticipated CMT1A trial in development, and whether muscle MRI will be included, at least in a subset of patients, is still being worked out. Ultimately, these decisions come down to what the FDA accepts as reasonable endpoints, and the agency has traditionally anchored to functional rating scales as primary endpoints. That is unlikely to change in the near term.

But the tofersen approval, which was supported in part by the impressive neurofilament changes seen in that trial, has clearly opened the door to greater regulatory interest in biomarker data. The more these markers can be validated against traditional functional endpoints, the more the FDA is likely to embrace them going forward. I think we are moving in that direction, even if it will take time.

Transcript edited for clarity.