Experimental Treatments for Huntington's Disease

Antisense oligonucleotides are a type of gene-silencing treatment being developed for Huntington’s disease. A few of these experimental therapies are currently in various stages of the clinical development process. Antisense oligonucleotides are artificially created nucleotides that bind to the HTT messenger RNA and prevents it from being translated into protein. In this way, the gene is “silenced,” or blocked, from creating toxic proteins.

ANX005 is a therapy being developed to slow disease progression in early-stage Huntington’s. The therapy is given directly into the bloodstream. In a Phase 2a clinical trial, ANX005 was associated with significantly greater clinical improvements in a subgroup of patients. There are plans for a future Phase 2b/3 trial.

CRISPR/Cas9 is an experimental gene-editing technique that could permit the “silencing” of the mutated HTT gene and prevent the formation of faulty protein in Huntington’s disease. This potential therapeutic approach is aimed at cutting out the mutated region of the HTT gene, thus permanently removing the mutation from the genome of every cell that is edited. The approach is currently in preclinical testing for Huntington’s.

Deep brain stimulation is a treatment for certain neurological conditions that is also being investigated for Huntington’s. It involves the surgical implantation of an electrode in the brain Wires passing through the neck connect the electrode to a stimulator in the chest. The stimulator is a small device that delivers a controlled electronic pulse to the brain. The approach is being tested in a trial for the treatment of chorea in Huntington’s patients.

Dextromethorphan/quinidine is an oral therapy that has been investigated to ease irritability in people with Huntington’s. A small Phase 3 trial missed its main goal, but there was a strong placebo effect. The therapy’s future clinical development is currently unclear.

Pepinemab, also known as VX15/2503, is an infusion therapy being developed by Vaccinex to slow Huntington’s progression. The therapy was tested in a Phase 2 clinical trial that failed to meet its main efficacy goals, but promising trends were observed in a certain group of patients. Advancement to Phase 3 testing is being considered

Pridopidine, previously known as ACR16 and Huntexil, is an experimental oral therapy being developed by Prilenia Therapeutics to slow the progression of Huntington’s. The therapy was tested in a Phase 3 clinical trial that failed to meet its main goal, but promising trends were observed in certain subgroups of patients.

PTC518 is a once-daily oral therapy being developed to slow Huntington’s disease progression. Interim data from a Phase 2a clinical trial showed that PTC518 was associated with trends of slowed disease progression relative to a placebo. There are plans for a future Phase 3 trial.

Resveratrol is a natural compound with antioxidant and neuroprotective properties that has been evaluated in a single clinical trial as a potential oral treatment to slow progression of Huntington’s disease. Trial results have not been reported to date.

Gene silencing by RNA interference (RNAi) is a potential therapeutic approach for the treatment of Huntington’s disease. The goal of this strategy is to reduce the amount of abnormal huntingtin protein being produced in cells. RNAi therapy is intended to deliver, with the help of adeno-associated viral vectors, micro RNAs that degrade HTT messenger RNA so that the amount of HTT protein decreases.

SOM3355 (bevantolol hydrochloride) is an experimental oral therapy being developed by SOM Biotech for Huntington’s-related chorea. After showing promise in a proof-of-concept Phase 2a trial, the therapy is being tested in Huntington’s patients within a Phase 2b trial.

Triheptanoin is a lab-made fatty molecule being developed as a potential oral treatment to slow the progression of early-stage Huntington’s disease. A Phase 2 trial failed to meet its main goal, but there were some promising signs suggesting that triheptanoin may help stabilize disease and slow brain shrinkage.