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.

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.

Resveratrol is a natural substance found in small quantities in grapes, blueberries, and cranberries, and is also available as a dietary supplement. Resveratrol directly or indirectly stimulates the activity of an enzyme called sirtuin type 1, which is known to upregulate key metabolic and anti-inflammatory pathways that protect cells from injury. Animal models of Huntington’s have shown the neuroprotective effects of resveratrol, and a Phase 3 trial in patients has been completed.

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 (also known as C7 oil) is an artificially produced triglyceride, a kind of fat, being developed to treat brain energy deficits by improving brain metabolism. Triheptanoin is thought to have an anaplerotic role, meaning that it can replenish substances involved in the tricarbolic acid cycle, a pathway used by cells to produce energy, providing an alternative source of energy to the brain. It is currently being studied in Huntington’s patients in a a Phase 2 trial.

VX15/2503 (pepinemab) is a monoclonal antibody that targets the protein semaphorin 4D (SEMA4D) developed to slow down and prevent neurodegeneration in patients with Huntington’s disease. VX15/2503 blocks the activity of SEMA4D, thereby preventing the activation of microglia and astrocytes, which are the main inflammatory cells in the brain. A completed Phase 2 trial showed good tolerability.