New Blood Test May Track Early Changes in Huntington’s Disease, Study Finds

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by Diogo Pinto |

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Two proteins present in the blood and brains of patients with Huntington’s disease may be used as biomarkers to detect the earliest changes caused by the disease, according to recent research.

The study, “Evaluation of mutant huntingtin and neurofilament proteins as potential markers in Huntington’s disease,” was published in Science Translational Medicine.

Led by researchers at the University College of London (UCL), the study reports on a new blood test that can track two proteins, mutant huntingtin (mHTT) and neurofilament light (NfL), even before scans can find any alterations in the brain.

Such a test would be useful in clinical trials seeking to detect the first treatment-related changes in patients with Huntington’s disease.

“Many people who develop Huntington’s report subtle signs such as with mood or coordination, in what’s called the prodromal stage before any changes can be detected by brain scans,” lead author Edward J. Wild, PhD, of the UCL Huntington’s Disease Center, UCL Institute of Neurology, said in a press release.

“We’ve found that blood testing could help identify groups of people with very early neurodegeneration to help us run clinical trials of drugs to prevent symptoms. We were surprised to find the blood test could pick up signs even before any evidence of neurodegeneration could be seen in brain scans,” Wild said.

The study recruited 80 participants from the National Hospital for Neurology and Neurosurgery/University College London/University College London Hospitals HD Multidisciplinary Clinic as part of an ongoing longitudinal, single-site CSF collection initiative called HD-CSF.

Of these patients, 40 had manifest (symptomatic) Huntington’s at different stages, 20 carried the mutation associated with the disease but had not yet been diagnosed, and 20 were healthy individuals used as a control group.

Researchers took samples of blood plasma and cerebrospinal (brain) fluid (CSF) and tested them for mHTT, the protein coded by the mutated HTT gene that causes the disease, and NfL protein, which often results from nerve cell damage.

The team then compared these results to those of clinical measures preformed on the same group of patients, including brain area volumes, using magnetic resonance imaging (MRI) scans and motor and cognitive tests.

The results revealed a strong correlation between NfL levels in the blood and brain and all clinical measures for mutation carriers. This link was not so strong for mHTT levels in the brain. Importantly, all these measures remained stable for up to eight weeks.

Brain levels of mHTT accurately distinguished between patients carrying the mutation and healthy individuals, while NfL concentrations, both in the brain and blood, distinguished between individuals carrying the mutation and those with manifest Huntington’s disease.

“mHTT and NfL concentrations in biofluids [blood and CSF] might be among the earliest detectable alterations in HD [Huntington’s disease],” the researchers wrote.

These findings may prove crucial for the success of an upcoming Phase 2 trial (NCT03342053) testing the investigational treatment RG6042 (formerly IONIS-HTTRx) in slowing the progression of the disease.

“We are living in a time of incredible advancement in the filed of neurodegeneration, and research in Huntington’s disease is paving the way towards interventions that can change people’s lives,” said co-author Filipe Brogueira Rodrigues, MD. “Developing tools to track biological and clinical changes, and identify candidates to participate in clinical trials, is vital for the success of such trials.”

Despite the encouraging results, researchers caution that the test is not yet ready to be used in patients.

“More research is needed to clarify potential of this test. We hope it can help to develop the first drugs to slow Huntington’s, and if they become available, then hopefully this test could help guide decisions on when to begin treatment,” said first author Lauren Byrne.