Biomarkers for Huntington’s Disease

Background

Huntington disease (HD) is an autosomal dominant neurodegenerative disease caused by a cytosine–adenine– guanine (CAG) expansion in the huntingtin gene (HTT) that codes for an abnormal polyglutamine tract. In carriers of the HD mutation, the disease manifests as an adult-onset disease but is preceded by an asymptomatic stage when cellular dysfunction and progressive neurodegeneration are already occurring in the brain. Therapeutic approaches targeting the cause of HD are currently in clinical development but may prove more effective if intervention is initiated prior to clinical onset. However, current methods of predicting age-of-onset are inaccurate (e.g. CAG repeat length in HTT has been correlated with age-of-onset yet it only accounts for 50–60% of the variability with other genetic and environmental factors reportedly playing a role). Availability of more accurate tools to predict disease onset and stratify stage of disease is required for the development and assessment of novel therapies to delay the onset or slow the progression of HD.

Technology Overview

Researchers at The University of British Columbia have identified certain combinations of biomarkers in cerebral spinal fluid of HD mutation carriers that define stage of disease progression (Fig.1) and also panels that may help improve existing methods for predicting age-of-onset. These markers provide a valuable diagnostic or prognostic tool and may also be useful for evaluating efficacy of novel therapeutic approaches during clinical trials.

Further Details:

Caron et al 2022

Stage of Development

The researchers are currently conducting further validation of the biomarkers in larger cohorts and assessing its added value in predicting age-of-onset.

Benefits

• Multi-marker CSF protein panels discriminate between different stages of disease ‑ AUC 0.91 ‑ 1.0 (Fig.1)
• Biomarker panels may improve predictions of disease onset
• Potential use in clinical trials to evaluate efficacy of novel therapeutics

Opportunity

Licensing opportunity.