Research Pipeline Overview

Basic Research

Basic research into what goes wrong in the brain in Huntington’s continues to provide insights into how the disease might be treated. The Huntington’s Disease Society of America funds basic research through its Coalition for the Cure and its Research Grants and Fellowship Program.  

Translational Research: Drug Discovery, Development, and Design

As targets are identified, existing drugs and supplements known to address that target are reviewed and drug development efforts are instituted.

Translational Research: Preclinical Testing

Promising drugs are tested in animal models such as drosophilia (fruit flies) and mice engineered to get Huntington’s Disease.  If the results are positive, a drug will be rigorously tested in one or more of the mouse models of HD.  If a drug is effective and side effects are tolerable, toxicology studies are done and the drug can proceed to clinical trials.

Clinical and Observational Trials

Once a drug is ready for testing in human patients, it must proceed though three phases of clinical trials. A drug must be shown to be safe, well-tolerated, and effective before the FDA will approve it for human use.  Visit our clinical trials page for more information about how trials work and to find a trial in your area.

Observational trials are also important.  By observing and testing people with the gene over time (the longitudinal approach) and groups of people at different stages of the disease (the cross sectional approach), researchers can discover and validate surrogate measures of disease progression.  Surrogate measures can reduce the time needed to conduct a Phase III clinical trial and get treatments to HD patients.  HD family members – gene positive, at risk, gene negative, and caregivers — can volunteer to participate in an observational trial like COHORT.

HDSA supports both kinds of trials through its grants to the Huntington Project (HP) and its assistance in the recruiting process. The Huntington Project works through the Huntington Study Group (HSG), an affiliation of approximately 62 clinical centers that plan and conduct trials aimed at treating HD.

HDSA has continued to increase its financial commitment to clinical trials and provide $550,000 annually to the Huntington Project. This funding enables HP to bring projects to the stage where they can apply for funding from the National Institutes of Health (NIH) to carry out these important trials.

A Dynamic Process

Although the research pipeline appears to proceed smoothly from basic research to clinical trials, in practice it is much more dynamic.  Translational researchers may need to go back to basic researchers to have questions answered.  A drug may show clear signs of efficacy in preclinical testing but have serious side effects or poor bioavailability requiring overly large doses to work.  Depending on its potential, there may be further efforts at developing the drug.  A drug that is successfully treating similar symptoms in another neurological disorder such as Alzheimer’s may move directly into clinical trials for HD patients. It is important for the HD community to know that Huntington’s research is going on in parallel.  Basic research, translational research, and clinical trials are all in progress.  There are more than two dozen drugs and supplements actively moving through the pipeline with dozens of others nominated for consideration.  When one critical question is answered, efforts turn to other questions.  When one drug fails, resources are quickly redirected to researching more promising ones.

To find out about the drugs and supplements currently moving through the research pipeline refer to the chart below — Therapies in the Pipeline.


Therapies In the Pipeline 2017/2018


Preclinical R & D Clinical Development
Target Validation Lead Optimization Safety and Manufacturing Phase I Phase II Phase III


Vaccinex: VX15 is a monoclonal antibody that binds to and blocks a molecule that may cause inflammation in the brain of individuals with HD.  The SIGNAL trial is a Phase II study to assess the safety, tolerability and effectiveness of VX15 in people at risk for developing HD.

HDAC Inhibitor

CHDI Foundation and BioMarin Pre-clinical data suggest that inhibition of histone deaceytlases (HDACs), may be beneficial in HD. CHDI Foundation and BioMarin are pursuing separate approaches.

Zinc Finger DNA-Binding Protein (ZFP)

Shire / Sangamo Focused on the development of sequence-specific ZFPs including ZFP Nucleases (ZFNs) for gene modification, and ZFP transcription factors (ZFP TFs), which can control gene expression and thus cell function.


Genzyme / Sanofi / Voyager Therapeutics A small hairpin RNA or short hairpin RNA (shRNA) is a sequence of RNA that makes a tight hairpin turn that can be used to silence target gene expression in Huntington’s disease via RNA interference (RNAi). Expression of shRNA in cells is accomplished by delivery of viral vectors — adeno-associated virus (AAV).


Spark Therapeutics A small hairpin RNA or short hairpin RNA (shRNA) is a sequence of RNA that makes a tight hairpin turn that can be used to silence target gene expression in Huntington’s Disease via RNA interference (RNAi). Expression of shRNA in cells is accomplished by delivery of viral vectors — adeno-associated virus (AAV)

Deep Brain Stimulation (DBS)

 Jan Vesper, M.D., Ph.D. University Clinic Dusseldorf, Germany Effects on chorea, dystonia and long-term effects on quality of life for HD patients will be examined in this study of deep-brain stimulation (DBS) in Europe.

Antisense Oligonucleotide Huntingtin Lowering

Roche and Ionis Pharmaceuticals Anti-sense oligonucleotides (ASOs) are a type of ‘huntingtin lowering’ or ‘gene silencing’ drug that bind to the huntingtin mRNA (message) and result in a decrease in the level of huntingtin protein. This drug lowers both expanded and normal huntingtin, an allele-non-specific approach. In December 2017 the Phase Ib/2a safety trial was reported as successful.


University of California at Davis Observational study for Huntington's disease at UC Davis. The purpose of this study is to learn about the rate of change of an individual with early stage Huntington's disease. Also, subjects who successfully complete PRE-CELL and meet future criteria, will be considered for HD-CELL (Stem-Cell therapy trial) that will use mesenchymal stem cells to deliver brain-derived neurotrophic factor (BDNF) to the brains of HD patients.

PDE10A Inhibitor (PF-02545920)

Pfizer PF-02545920 is a drug originally developed for the treatment of schizophrenia. It acts as a phosphodiesterase (PDE) inhibitor selective for PDE10A, a protein that is expressed predominantly in the striatum. This study (Amaryllis) tested the drug in HD patients but has been terminated because it failed to show benefit.

Cysteamine (RP103)

Raptor Pharmaceuticals Cysteamine may exert its beneficial effects by increasing the secretion of brain-derived neurotrophic factor (BDNF) in the brain.  BDNF levels are diminished in HD and increased secretion of BDNF could be neuroprotective.

Laquinimod (Legato-HD)

Teva Pharmaceuticals Laquinimod modulates several significant pathways common to key neurodegenerative disease. More specifically, it modulates the immune cell lineages in the periphery and in the central nervous system. It can be thought of as an anti-inflammatory drug for the brain.

Pridopidine (Pride HD)

Teva Pharmaceuticals Pridopidine is an experimental drug candidate belonging to a class of agents known as dopidines, which act as dopaminergic stabilizers in the central nervous system. Pridopidine has shown promise in improving total motor symptoms in HD patients


TEVA Pharmaceuticals Deutetrabenazine is an investigational drug with the same mechanism of action as tetrabenazine to treat the involuntary movements (chorea) of Huntington’s disease. Deutetrabenazine is broken down by the body more slowly than TBZ. These differences may mean that: 1) the drug may be taken fewer times per day than tetrabenazine; 2) a lower dose may be as effective at controlling chorea; and 3) improve how well the body reacts to the drug, compared to tetrabenazine, with potentially less side effects plus good chorea control.


PTC TherapeuticsSmall molecules are in development that could interfere with splicing, with the goal of changing how the HD gene produces the huntingtin RNA message and lowering harmful protein levels. Ideally these would be delivered orally but could reach the brain.


UniQUREAMT-130 is a drug that uses a type of harmless virus called an AAV5 vector, which carries a micro-RNA designed to silence the huntingtin gene. The therapeutic goal is to inhibit the production of the mutant protein by delivering this virus to the brain.


Ipsen PharmaceuticalsTriheptanoin is a type of oil called a triglyceride that is being tested as a dietary supplement in a small study in France and the Netherlands. The primary goal is to test whether it can prevent atrophy of brain areas affected by HD.


Azevan Pharmaceuticals SRX246 is an investigational drug to treat symptoms of anxiety and aggression in early stage HD patients. It acts by blocking vasopressin receptor 1a which plays a role in regulation of emotions.


SOMBIOTECH SOM3355 is a vesicular monoamine transport (VMAT) inhibitor that acts similarly to tetrabenazine by interfering with how dopamine messages are passed between neurons. This company is focused on treating rare diseases by repurposing drugs that have already been developed and researched.


Wave Life SciencesAnti-sense oligonucleotides (ASOs) are a type of ‘huntingtin lowering’ or ‘gene silencing’ drug that bind to the huntingtin mRNA (message) and result in a decrease in the level of huntingtin protein. Wave's drug takes an allele-specific approach, lowering only harmful huntingtin by finding tiny genetic changes called SNPs on the expanded gene.


Wave Life SciencesWave has developed two different ASOs using the same approach. These studies will run in parallel and will test the safety and tolerability in a small group of people with early HD.


Prosensa/BiomarinAnti-sense oligonucleotides (ASOs, or AONs) are a type of ‘huntingtin lowering’ or ‘gene silencing’ drug that bind to the huntingtin mRNA (message) and result in a decrease in the level of huntingtin protein. Biomarin is developing

Tetrabenazine  (Xenazine)

LundbeckTetrabenazine is used to treat the involuntary movements (chorea) of Huntington’s disease. Tetrabenazine is a Vesicular Monoamine Transporter 2 (VMAT2) inhibitor, and  acts by decreasing the levels of the neurotransmitter dopamine in the synapse (space between neurons). In 2008 it was the first HD drug to be approved by the U.S. Food and Drug Administration (FDA).
FDA Approval
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