MedicalResearch.com Interview with:
Dr Edward Wild PhD
MRC Clinician Scientist
Huntington’s Disease Centre
UCL Institute of Neurology
Honorary Consultant Neurologist
National Hospital for Neurology & Neurosurgery,
MedicalResearch.com: What is the background for this study?
Response: Having a readily accessible and sensitive biomarker, that is representative of ongoing neuropathology, could facilitate therapeutic development for Huntington’s disease. Neurofilament light (NfL) protein is one of the component that makes up the cytoskeleton of neurons. It is released when neuronal damage or death occurs and can be quantified in blood.
MedicalResearch.com: WWhat are the main findings?
Response: We carried out a retrospective cohort analysis of samples from the TRACK-HD study – a multisite longitudinal observational study of HD patients. NfL was quantified in plasma from 298 participants at baseline and follow-up. NfL was significantly higher in HD compared to healthy controls and increased with disease stage. Baseline levels of plasma NfL predicted clinical progression, including cognitive and functional decline, and the rate of global and regional brain atrophy. Premanifest individuals who converted to manifest Huntington’s disease in the three years of the study had significantly higher levels of plasma NfL at baseline. These associations remained significant after adjustment for the combined interaction of age and CAG, currently the best predictor of age of onset of Huntington’s disease. In a separate cohort, levels of NfL in plasma and CSF were highly correlated.
MedicalResearch.com: What should clinicians and patients take away from your report?
Response: Despite decades of research, no substance in blood has shown any power to predict disease progression of Huntington’s disease. In addition, no substance has been shown to be increased as in premanifest subjects over 10 years from their predicted onset suggesting it may have potential for detecting the earliest signs of HD before overt symptoms manifest.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: We hope that quantifying NfL will be incorporated into all future observational studies of Huntington’s disease and potentially retrospectively where blood or CSF samples have been banked. We feel it should also be used in current and future clinical trials as an efficacy marker to assess whether a drug is slowing neuronal damage, at the very least as an exploratory end point.
MedicalResearch.com: Is there anything else you would like to add?
Response: At the moment we do not have enough information for this blood test to be of clinical relevance and prognosis of a patient. A lot more research needs to be done before it could be use on an individual basis in the clinic.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Citation: Lauren M Byrne, Filipe B Rodrigues, Kaj Blennow, Alexandra Durr, Blair R Leavitt, Raymund A C Roos, Rachael I Scahill, Sarah J Tabrizi, Henrik Zetterberg, Douglas Langbehn, Edward J Wild. Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington’s disease: a retrospective cohort analysis. The Lancet Neurology, 2017; DOI: 10.1016/S1474-4422(17)30124-2
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