Experimental Treatments

Huntington’s disease is an inherited progressive neurodegenerative disorder, caused by a mutation in the huntingtin (HTT) gene. The mutation results in an abnormal, toxic HTT protein being produced that aggregates inside nerve cells in the brain, leading to their death. This causes problems with movement, cognition, and behavior, as well as various psychiatric disorders.

Research is currently ongoing to find a cure for Huntington’s disease and to develop novel therapies to delay the progression and better manage the symptoms of the disease. Some examples of treatments currently in development are discussed below.

Gene silencing therapies

Gene silencing therapies act to reduce or prevent the abnormal HTT protein from being made. The approach targets the mRNA or the molecule that carries the instructions contained in a gene to the protein-making machinery of the cell. This can either be by preventing the mRNA from being produced, or by stopping it from reaching the protein-making machinery. This should prevent or slow the damage to nerve cells by reducing the levels of toxic HTT.

IONIS-HTTRx is an investigational antisense therapy, originally developed by Ionis Pharmaceuticals and now licensed to Roche. It is a complementary molecule to the HTT mRNA, which binds to the mRNA and flags it for destruction. Recent results from a Phase 1/2a clinical trial (NCT02519036) suggest that the therapy is safe and can reduce levels of the toxic HTT protein in a dose-dependent manner. An open-label extension study (NCT03342053) is enrolling patients completing the first trial, to assess the long-term safety and efficacy of the therapy.

AMT-130, being developed by uniQure, is a treatment that is still in preclinical development. It is an artificial microRNA targeting the HTT mRNA. The body normally produces microRNAs against specific genes to regulate protein levels. AMT-130 uses the system already present in the body to prevent the mutated HTT protein from being produced. With positive proof-of-concept preclinical trial results, uniQure hopes to submit an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) in 2018 in order to begin human clinical trials with AMT-130.

Two additional HTT gene silencing therapies by Wave Life Sciences are being tested in Phase 1/2 clinical trials: WVE-120101 (PRECISION-HD1, NCT03225833) and WVE-120102 (PRECISION-HD2, NCT03225846). Both trials are currently recruiting participants at sites in Canada and Poland.

Other potential HTT gene silencing therapies are in development but not yet at clinical trial stage. Voyager Therapeutics is collaborating with Sanofi Genzyme on the development of VY-HTT01.  Spark Therapeutics also intends to develop a gene therapy program targeting Huntington’s disease. Sangamo and Shire are collaborating to develop a therapy to repress HTT gene expression.

Neuronal protection and anti-inflammatory therapies

Several therapies are in development that aim to prevent the damage to and death of nerve cells in the brain due to toxic HTT protein accumulation. This can be done by inhibiting genes that can trigger cell death or by reducing inflammation, which can cause further damage.

VX15/2503, being developed by Vaccinex, is an antibody against the protein SEMA4D. SEMA4D is involved in signaling processes leading to neuroinflammation and cell death. Antibodies are proteins designed to interact with a specific target, and VX15/2503 binds to and blocks the activity of SEMA4D. A Phase 2 clinical trial (NCT02481674) called SIGNAL is currently ongoing in the U.S., with initial trial results suggesting that the treatment is safe and may be effective in preserving brain structure in Huntington’s patients.

Laquinimod, being developed by Teva Pharmaceuticals, is thought to reduce neuroinflammation in Huntington’s patients. The safety and efficacy of lacquinimod are being investigated in an ongoing Phase 2 clinical trial (NCT02215616) called LEGATO-HD.

Huntexil (pridopidine), being developed by Teva Pharmaceuticals, is a dopamine stabilizer. Dopamine is a signaling molecule in the brain involved in motor control, that can be abnormally high in Huntington’s patients, leading to damage and neurodegeneration. Huntexil can inhibit dopamine-controlled processes, therefore, improving motor symptoms and slowing disease progression. It does this by enhancing the secretion of BDNF (brain-derived neurotrophic factor, a protein that promotes the survival and growth of nerve cells). Several clinical trials have been completed and some are still ongoing to further test Huntexil in Huntington’s patients.

SBT-20, being developed by Stealth Biotherapeutics, may help reduce nerve cell death by improving mitochondrial function in the brain. Mitochondria produce energy for the cells but can be dysfunctional in Huntington’s disease, leading to decreased energy and a build-up of toxic by-products. A Phase 1/2 clinical trial (EudraCT Number: 2016-003730-25), called CHALLENGE-HD, is currently ongoing in the Netherlands.

Symptomatic therapies

SRX246 is being developed by Azevan Pharmaceuticals to treat the behavioral symptoms of Huntington’s such as anxiety and depression. It blocks vasopressin receptor 1a, a protein involved in emotion regulation. A Phase 2 trial (NCT02507284), called STAIR, is currently recruiting patients with Huntington’s disease in the U.S.

Several clinical trials to assess whether certain supplements can help manage the symptoms of Huntington’s are currently ongoing. These include Triheptanoin oil (in Phase 2 clinical trial, NCT02453061) and Resveratrol (in Phase 3 clinical trial, NCT02336633).

Finally, a clinical trial (NCT02535884) is currently recruiting participants in Austria, Germany, and Switzerland, to assess how deep brain stimulation (DBS) can improve chorea in Huntington’s patients.


Huntington’s Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.