Biofluid Biomarkers Hold Promise for the Future of Huntington Disease

By Erica Slaughter

Huntington disease (HD), a genetically dominant trinucleotide repeat disorder resulting from cytosine-adenine-guanine (CAG) repeats within the huntingtin (HTT) gene, has a near-full pene- trance and onset of symptomatology and neuronal loss typically by the third decade of life.

A neuropathological hallmark of HD is cortical atrophy, as indicated in postmortem assessments. These studies have been limited, however, because the assessments were performed on tissue of neuropathological grades 2-4. Cortical atrophy at early stages of HD, before symptoms develop, remains unclear.

There have been few reliable and quantifiable indicators of disease severity, progression, or phenotype, which has limited therapy development. Currently, there are no disease-modifying medications and few interventions available to effectively alleviate symptoms. The lack of indicators of pathobiological processes at the molecular level has limited the ability to prove efficacy and safety in clinical trials.