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Blood Test Predicts Onset of Huntington's Disease

By LabMedica International staff writers
Posted on 21 Jun 2017
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Huntington's disease (HD) is a fatal genetic neurological disease. It usually develops in adulthood and causes abnormal involuntary movements, psychiatric symptoms and dementia and approximately 10,000 people in the UK have HD with around 25,000 at risk.

Huntington's disease is caused by a single known genetic mutation, and each child of a carrier of the mutation has a 50% chance of inheriting the disease. Currently, the best biomarkers available are measured with neuroimaging or cerebrospinal fluid, which are more difficult and expensive to obtain than a blood test.

An international team of scientists collaborating with the University College of London (UK) investigated whether neurofilament light protein NfL (also known as NF-L) in blood is a potential prognostic marker of neurodegeneration in patients with Huntington's disease. The team used a blood test to measure NfL, a protein released from damaged brain cells, which has been linked to other neurodegenerative diseases but has not been studied in the blood of Huntington's disease (HD) patients before. The international project followed 366 volunteers for three years.

Neurofilament light protein (NfL) were measured in plasma with an ultrasensitive single-molecule array method, the NF-Light assay and transferred onto the Simoa platform with a home-brew kit. All NfL values were within the linear ranges of the assays. A London-based independent cohort of 37 participants (14 controls, three huntingtin gene (HTT) mutation carriers with premanifest disease and 20 participants with manifest Huntington's disease underwent cerebrospinal fluid (CSF) and plasma collection standardized for diet, time of day, clinical procedures, and processing. NfL concentrations in CSF were quantified with the UmanDiagnostic’s enzyme-linked immunosorbent assay.

The scientists found that levels of the brain protein were increased throughout the course of HD, even in carriers of the HD genetic mutation who were many years from showing symptoms of the disease. HD mutation carriers had neurofilament concentrations that were 2.6 times that of the control participants, and the level rose throughout the disease course from premanifest to stage 2 disease. In the group who had no symptoms at the start of the study, the level of neurofilament predicted subsequent disease onset, as volunteers with high neurofilament levels in the blood at the start were more likely to develop symptoms in the following three years.

Edward J. Wild, MB BChir, PhD, the lead author of the study, said, “We have been trying to identify blood biomarkers to help track the progression of HD for well over a decade, and this is the best candidate that we have seen so far. This is the first time a potential blood biomarker has been identified to track Huntington's disease so strongly.” The study was published on June 7, 2017, in the journal Lancet Neurology.

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