Every year, more than 4.2 million people in the UK suffer nerve damage from car crashes, surgery, or birth complications—and there is no blood test to tell doctors whether the injury will heal on its own or requires urgent surgical repair. This matters because mild nerve injuries (neurapraxia) resolve with time, but severe ones (axonal degeneration) must be repaired immediately. Without a reliable diagnostic test, patients often face delays that permanently cost them movement, sensation, or freedom from chronic pain. Currently, clinicians have no way to distinguish the two forms at the bedside. The researchers have already shown that a protein called neurofilament light chain (NfL), released when nerve fibres break down, accurately signals nerve damage in rats. This project will test whether the same protein works in humans, by measuring NfL levels in blood samples from patients undergoing elective nerve surgery and comparing them to the actual volume of nerve damage seen under a microscope. If successful, the test could be rapidly adopted in NHS hospitals—NfL testing is already used routinely for traumatic brain injury. It would give surgeons a fast, affordable tool to triage nerve injuries, reducing delays, unnecessary surgeries, and life-long disability.
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There is a clear unmet clinical need for a blood test to identify and quantify peripheral nerve degeneration. Nerve damage is estimated to affect more than 4.2 million people annually and can be caused by traumatic injury (e.g. road traffic accidents), surgical procedures (e.g. tumour removal), and birth complications (e.g. obstetric brachial plexus palsy) but often nerve damage is initially undiagnosed. Furthermore, even when a loss of nerve function is identified, there is no diagnostic test to identify whether this is the mild form of nerve injury - neurapraxia (temporary conduction block which will resolve with time), or is more severe (permanent degeneration of axons) and therefore may require surgical intervention. Due to the complexity of this clinical differential diagnosis, there is often a significant delay in identifying those patients with nerve degeneration that require specialist referral and microsurgical repair. Such delays are seriously detrimental to functional recovery because nerves have a limited capacity for regeneration which fades with time; ideally injured nerves should be repaired immediately. The consequences for patients of poor functional recovery can be life changing and include permanent loss of sensation and movement, chronic pain, mental illness and significant personal, societal and economic impact. Therefore, there is an urgent need for a valid, accurate and reliable test that could be used to identify the presence of nerve degeneration at the time of injury. Currently there is no such test available and therefore management is often delayed causing significant additional morbidity. Recently our research team demonstrated that the serum concentration of neurofilament light chain (NfL), a protein that is released when axons degenerate, provides an accurate indication of the presence and severity of peripheral nerve damage in rats. The aim of this project is to progress this work along the translational pathway towards establishing a new diagnostic test, by assessing the feasibility of using NfL as a biomarker in human nerve injury. The approach will be informed by our previous animal study and will determine the correlation between serum NfL and the volume of axonal damage in patients undergoing elective nerve surgery. Serum NfL testing is already used widely in hospitals as a rapid, affordable and effective diagnostic tool in traumatic brain injury and acquired neuropathies. Therefore if this project shows that serum NfL is a suitable biomarker for identifying peripheral nerve damage it could easily be incorporated into clinical diagnostic pathways to address this unmet need. Furthermore, our team has already established the ethical approval and started to collect suitable nerve and blood samples. This project will (1) assess nerve tissue histologically in order to measure the volume of axonal degeneration, (2) measure serum NfL concentration in corresponding blood samples from the same patients, then (3) integrate these data to test feasibility and underpin the next stage of development.
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