New Treatments & Clinical Trials for Huntington's Disease

Huntington's disease is a hereditary neurodegenerative condition caused by an expanded CAG repeat in the HTT gene, leading to the progressive death of neurons in the striatum and cortex. It causes movement problems (chorea), cognitive decline, and psychiatric symptoms, typically emerging between ages 30 and 50. The condition is uniformly fatal, and until recently all treatments were purely symptomatic.

What's actually going on in research

Antisense oligonucleotides (ASOs) that reduce the production of mutant huntingtin protein remain the most advanced disease-modifying approach. Tominersen, an ASO delivered intrathecally, showed early promise but a large trial was halted due to an unfavorable benefit-risk profile at higher doses; smaller dose exploration continues. Allele-selective ASOs and siRNA approaches targeting only the mutant copy are in development, as are gene editing strategies. Trials addressing neuroinflammation and synaptic dysfunction are also active.

What to know before you search

Eligibility for most disease-modifying trials requires confirmed HTT CAG expansion, early-stage diagnosed or pre-manifest status, and ability to receive intrathecal or IV study drug.

What types of trials are currently open

• Huntingtin-lowering trials — Testing ASOs and siRNA approaches to reduce mutant huntingtin protein in early and pre-manifest HD.
• Gene editing trials — Early-phase CRISPR and zinc finger nuclease programs targeting the expanded CAG repeat in HTT.
• Neuroprotection trials — Evaluating drugs targeting mitochondrial function, synaptic health, and neuroinflammation to slow neuron loss.
• Psychiatric symptom trials — Testing interventions for depression, anxiety, and irritability in diagnosed HD patients.
• Pre-manifest HD studies — Enrolling mutation carriers before symptom onset to identify biomarkers and test preventive interventions.