The Huntington’s Disease Research Pipeline
A research “pipeline” is the process of creating, testing, and approving a new drug for use in humans. HDSA funds researchers and doctors doing Huntington’s Disease (HD) research at different stages along the pipeline, and collaborates with industry partners to bring information about clinical trials to the public. We do not fund clinical trials but through our fellowship programs we support human-centric research.
Preclinical research
The research pipeline involves basic research into what goes wrong in the brain in Huntington’s disease, to identify targets for treatment. Then, new and existing drugs can be created or repurposed to address that target, and the drug development process begins.
Promising drugs are tested in models such as cells grown in a dish, fruit flies, and mice that are engineered to get Huntington’s disease. If the results are positive, a drug will be rigorously tested in more mouse models and usually in primates. If a drug reaches its target, side effects are tolerable, and improvements are seen in animals, the drug can proceed to clinical trials in people.
Clinical Trials of Drugs
Once a drug is ready for testing in human patients, it must proceed through three phases of clinical trials. Phase 1 is a small trial (20-50 people with HD) testing safety. Phase 2 is a medium sized trial (50-200 people with HD) testing safety and effects of the drug on the body. Phase 3 is a large trial (200-1000 people) testing whether the drug helps with symptoms. A drug must be shown to be safe, well-tolerated, and effective before the FDA will approve it for human use.
Observational trials
Observational trials do not involve testing a drug – they simply look at human behavior and biology to learn more about HD, through neurological exams, cognitive tests, and blood or spinal fluid donations. By observing and testing people with the HD gene over time and at different disease stages, researchers can discover what is changing inside the brain and body before and after the onset of HD symptoms. This is particularly important for the design of future trials that will need to measure the effectiveness of drugs before symptoms even appear.
HD family members – gene positive, at risk, gene negative, and caregivers — can volunteer to participate in an observational trial like Enroll-HD.
A Dynamic Process
Although the research pipeline appears to proceed smoothly from pre-clinical 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 require 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 may move directly into clinical trials for HD patients. It is important for the HD community to know that many types of Huntington’s research are 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 experimental medications currently moving through the research pipeline refer to the chart below. Note that this chart is focused on drugs and supplements. There are also studies underway that are focused on devices, non-drug interventions, and support systems to change brain and behavioral patterns and improve quality of life for people with HD. Examples include deep brain stimulation, dietary regimens, coaching, physical therapy, exercise, and psychotherapy.
If a trial is noted as currently recruiting in the United States or Canada, you may find more information about it by going to HDSA’s clinical trials matching service, HD Trialfinder. HDSA strives to maintain updated listings and descriptions of the trials below. If you have questions or comments, please reach out to Dr. Tamara Maiuri, Associate Director of Research and Patient Engagement, tmaiuri@hdsa.org.
Therapies In the Pipeline 2025
Basic
Research Preclinical R & D Clinical Development
Research Preclinical R & D Clinical Development
Target Validation
Lead Optimization
Safety and Manufacturing
Phase I
Phase II
Phase III
Xenazine/ tetrabenazine
Lundbeck:
Tetrabenazine 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) for HD.
Austedo/ deutetrabenezine
Teva:
An oral medication that reduces involuntary movements in HD by lowering dopamine levels in the brain. It works by blocking VMAT2, a protein that helps store and release dopamine. Austedo requires less frequent dosing than it's predecessor drug, and is FDA-approved.
Ingrezza/ valbenezine
Neurocrine:
Like Austedo, Ingrezza is an oral medication that treats chorea in HD by blocking VMAT2, a protein involved in controlling dopamine release. By reducing dopamine activity, it helps manage involuntary movements. Ingrezza is FDA-approved and taken once daily.
Pridopidine
Prilenia:
An oral drug that aims to protect brain cells by activating a protein called Sigma-1 Receptor (S1R), which supports cell survival and function. Although it has been proven safe, a recent Phase 3 trial did not meet its main goals. Prilenia is seeking regulatory approval for pridopidine in Europe, and continuing discussions with the FDA.
Cellavita HD
Azidus:
A stem cell therapy being tested in Brazil that uses cells from the soft tissue inside teeth. These cells may help repair brain damage and reduce inflammation in HD. The treatment is given through intravenous (IV) infusions.
Tominersen
Roche:
An investigational drug that lowers huntingtin protein by targeting its genetic message (HTT mRNA) for breakdown. It’s delivered directly into the spinal fluid by lumbar puncture. After a halted Phase 3 trial in 2021, a new Phase 2 study (GENERATION-HD2) began in 2023 and is ongoing, with recent updates adjusting the dosing strategy.
Votoplam (formerly PTC-518)
PTC Therapeutics and Novartis: An oral drug that lowers huntingtin protein by changing how the HTT gene’s message is processed, leading to its breakdown. Unlike some other therapies, it can cross the blood-brain barrier and doesn’t require spinal injections. Currently in a Phase 2a trial, early results show it reduces huntingtin levels, is safe, and may show promise for improving symptoms (a Phase 3 trial will be needed to know for sure, plans for which are in the works).
SKY-0515
Skyhawk: An oral "RNA splicing" drug that aims to lower huntingtin protein by altering the HTT gene’s message. It may also affect another protein (PMS1) linked to CAG repeat expansion, a key feature in HD. After showing safety and HTT-lowering effects in early trials, a Phase 2/3 study is expected to begin in mid-2025.
SRX246
Azevan:
An oral drug that blocks a brain receptor involved in stress and aggression (vasopressin V1a receptor). In a completed Phase 2 trial (STAIR), it showed positive effects on irritability and aggression in people with HD. While it received orphan drug and fast track status, further development plans have not been announced.
ANX005
Annexon:
ANX005 is an intravenous antibody that blocks C1q, a protein that activates part of the immune system thought to harm brain cell connections in HD. By calming this immune response, it aims to protect synapses. A Phase 2a study was completed, but the company is currently prioritizing other programs.
MBF-015
Medibiofarma: MBF-015 is an oral small molecule that blocks HDAC1 and HDAC2—enzymes that affect gene activity in the brain. By doing so, it may support healthy gene expression and improve brain cell communication in HD. A small Phase 2a trial has been completed in Europe.
Pepinemab (VX15)
Vaccinex:
Pepinemab is an antibody given by IV that targets SEMA4D, a molecule involved in brain inflammation. By blocking SEMA4D, it may help reduce harmful immune activity in HD. A Phase 2 trial (SIGNAL) did not meet its main goals, but there were hints of benefit in people with more advanced HD. Further development is currently uncertain.
Triheptanoin
Ultragenyx: Triheptanoin is an oral synthetic fat designed to improve energy production in brain cells, which may be impaired in HD. A Phase 2 study found no clear benefit over 6 months, but longer-term treatment showed signs of motor stability and reduced brain atrophy. More research is needed to confirm these effects.
SOM3355
SOM Biotech:
SOM3355 is an oral drug that reduces dopamine release by blocking VMAT2, helping to control involuntary movements (chorea) in HD. Originally developed as a heart medication, it’s being repurposed to offer a potentially safer alternative to existing VMAT2 inhibitors. Phase 2 trials have been completed.
Nicotinamide riboside
Oslo University Hospital: Nicotinamide riboside (NR) is a form of vitamin B3 being tested as a potential treatment for HD. It helps boost levels of NAD+, a molecule essential for cell energy and repair, which is often depleted in HD. Researchers hope that restoring NAD+ levels can improve brain cell health and slow disease progression. A Phase 2 clinical trial (NAD-HD) is currently underway.
N-Acetyl Cysteine (NAC)
Western Sydney Local Health District: N-Acetyl Cysteine (NAC) is an antioxidant being tested to help protect brain cells in people with early signs of HD. It may reduce oxidative stress and support mitochondrial function, both of which are disrupted in HD. A Phase 2 trial (NAC-preHD) is underway to assess its effects in people who carry the HD gene but don’t yet have noticeable symptoms.
WVE-003
Wave Life Sciences:
WVE-003 is an allele-specific antisense oligonucleotide (ASO) designed to selectively lower mutant huntingtin (mHTT) protein by targeting a genetic variant found only on the mutant copy of the gene. It’s delivered by lumbar puncture every 8 weeks. Phase 1b/2a trial (SELECT-HD) is ongoing to evaluate safety and early signs of benefit.
AMT-130
uniQure: AMT-130 is a one-time gene therapy that uses a harmless virus to deliver genetic material designed to lower levels of the huntingtin protein, which builds up in HD and harms brain cells. It’s injected directly into deep brain areas involved in movement using MRI-guided surgery. This early-stage trial is testing safety and how well it may work over time.
VO659
Vico: VO659 is an experimental drug that aims to lower production of the harmful huntingtin protein in HD by blocking the genetic message that creates it, without destroying that message the way that some other huntingtin-lowering drugs work. It's given through a spinal injection every two months. Early-stage trials are underway to test safety and potential effects on HD symptoms.
SPK-10001
Spark Therapeutics: SPK-10001 is a one-time gene therapy that uses a harmless virus to deliver genetic instructions that lower the amount of huntingtin protein, which is harmful in HD. Like uniQure’s AMT-130, it’s delivered directly into movement-related areas of the brain through MRI-guided surgery. Early testing (Phase 1/2) is underway to assess safety and potential benefits.
ALN-HTT02
Alnylam: ALN-HTT02 is an investigational RNA-based drug that aims to lower levels of the huntingtin protein by blocking its genetic instructions. It’s delivered directly into the spinal fluid by lumbar puncture and is designed to spread broadly throughout the brain, with long-lasting effects that may allow less frequent dosing. A Phase 1 trial is underway to test safety and how long the drug lasts in the body.
LPM3770164 / LY03015
Luye Pharma: LY03015 is a new oral drug being tested to treat Huntington’s disease (HD) and tardive dyskinesia (TD). It works in two ways: first, by lowering dopamine activity in the brain to reduce involuntary movements; and second, by activating a protein called Sigma-1 Receptor, which may protect brain cells and improve thinking. A Phase 2 trial for TD is underway in China, and early studies suggest it could be helpful for HD as well.
ER2001
ExoRNA: ER2001 is an experimental treatment that uses a specially engineered genetic package to deliver huntingtin-lowering instructions directly to brain cells. It’s based on a plasmid (a circular piece of DNA) that produces both a tag to help it find and enter neurons, and a small interfering RNA (siRNA) designed to reduce production of the huntingtin protein. ER2001 is administered through intravenous infusion. A Phase 1 clinical trial is currently underway in China to assess its safety and effectiveness in individuals with early-stage HD.
ATL-101
Atalanta: ATL-101 is a new experimental treatment that aims to lower the harmful huntingtin protein in HD using a specially designed RNA molecule that spreads widely and lasts a long time in the brain and spinal cord. The drug will be given by spinal injection, and early safety testing (Phase 1) is expected to begin soon.
Latus Bio
Latus Bio: Latus Bio is developing a one-time gene therapy for HD that aims to slow the disease by reducing a protein called MSH3, which contributes to harmful genetic changes over time. The treatment uses a specially engineered viral delivery system with an advanced design to reach the right brain cells efficiently, while avoiding unwanted effects in other tissues. This therapy is currently in preclinical testing, with clinical trials expected to begin soon.
HX127
Huntx: HX127 is an oral drug in development that targets a brain enzyme to restore healthy transport of BDNF, a protein that supports brain cell health. By improving how brain cells communicate, it may help with movement, thinking, and mood in HD. It’s currently in preclinical testing, with plans to begin human trials in 2026.
Harness Therapeutics
Harness Therapeutics: Harness is developing an antisense oligonucleotide (ASO) designed to increase levels of FAN1, a protein that may help slow the genetic changes that drive HD. By boosting FAN1, the treatment could delay disease onset or progression. This therapy is still in the early research phase.
LoQus23 Therapeutics
LoQus23 Therapeutics: LoQus23 is developing an oral drug that lowers levels of MSH3, a protein linked to harmful DNA changes that drive HD progression. By reducing MSH3, the therapy aims to slow or stop the genetic instability at the root of HD. They are currently testing drugs in animal models.
Alchemab
Alchemab: Alchemab is developing an antibody therapy designed to recognize and bind to the toxic form of the huntingtin protein (mHTT) found outside of brain cells. This protein is thought to spread and worsen Huntington’s disease. The antibody was discovered by studying people who appear resilient to neurodegenerative conditions, with the idea that their immune systems may naturally produce protective antibodies. In early lab studies, this antibody reduced mHTT clumping.
Incisive Genetics
Incisive Genetics: Incisive Genetics is developing a CRISPR-based gene editing therapy that aims to selectively target and modify the mutant huntingtin (mHTT) gene. By focusing on genetic markers (SNPs) found only on the faulty copy of the gene, the goal is to reduce harmful protein production without affecting the healthy gene. This program is in the preclinical research stage.
Life Edit
Life Edit: LETI-101 is a CRISPR-based gene editing therapy designed to selectively turn off the mutant huntingtin gene while leaving the healthy copy untouched. It uses a harmless virus to deliver the gene editor throughout the brain. In early lab studies, it greatly reduced harmful protein levels and was well tolerated in animals. LETI-101 is Life Edit’s lead HD program and is currently in preclinical testing.
ReviR Therapeutics
ReviR Therapeutics: ReviR Therapeutics is developing an oral small molecule that targets both the huntingtin gene and PMS1, a protein involved in harmful DNA changes in HD. It works by changing how the gene’s message is processed, leading to less production of these proteins. In early studies, the drug reached the brain well, lowered huntingtin levels, and showed signs of slowing the DNA changes linked to disease progression.
Origami Therapeutics
Origami Therapeutics: Origami is developing a small-molecule drug that helps remove the harmful form of the huntingtin protein while leaving the healthy version alone. Using patient-derived brain cells, their approach is designed to prevent or slow damage in HD by directly targeting the root cause—misfolded, toxic proteins. Their lead drug is still in preclinical testing.
Passage Bio
Passage Bio: Passage Bio is developing a gene therapy for HD that aims to reduce the production of the harmful huntingtin protein. This therapy uses a harmless virus to deliver genetic instructions directly to brain cells. Currently in the preclinical stage, Passage Bio is collaborating with GEMMA Biotherapeutics to advance this program, with plans to initiate clinical trials in the future.
VTx-003
VectorY: VTx-003 is an experimental gene therapy for Huntington’s disease that delivers genetic instructions to brain cells, enabling them to produce a therapeutic antibody. This antibody is designed to bind specifically to the harmful form of the huntingtin protein, promoting its clearance while preserving the normal version essential for brain function. The therapy would entail a one-time viral delivery, and is currently in the discovery phase.
INT41
Vybion: INT41 is an experimental gene therapy for Huntington’s disease that uses a harmless virus to deliver a specialized antibody fragment, called an intrabody, directly into brain cells. This intrabody is designed to bind to and neutralize toxic fragments of the mutant huntingtin protein, preventing them from disrupting normal gene activity. In animal studies, INT41 has shown promise in improving both movement and cognitive functions. The therapy has received Orphan Drug Designation from the FDA and is currently in preclinical development.
Arvinas
Arvinas: Arvinas is developing an oral treatment for Huntington’s disease (HD) using its PROTAC® technology. This approach aims to selectively eliminate the harmful mutant huntingtin protein (mHTT) while preserving the normal version essential for brain health. Unlike some therapies that require direct brain injections, Arvinas' PROTACs are designed to be taken by mouth and to cross the blood-brain barrier to reach affected areas. In early studies, these compounds have shown promise in reducing mHTT levels in mouse brain without impacting the healthy protein. The treatment is currently in preclinical development.
EHP-102
Emerald Health Therapeutics: EHP-102 is an oral drug in development for HD, made from a non-psychoactive compound found in cannabis. It’s designed to protect brain cells and reduce inflammation. In early lab studies, it helped prevent damage and supported nerve cell growth. The drug has received orphan drug status in both the U.S. and Europe and is currently in preclinical testing.
Pfizer
Pfizer: Pfizer is developing an oral drug for HD that targets MSH3. MSH3 plays a role in making CAG gene repeats get worse over time. By lowering MSH3, the drug aims to slow or stop these harmful changes, which may delay disease progression. The treatment is still in early testing.
Anima Biotech / Takeda
Anima Biotech / Takeda: Anima Biotech is developing an oral drug that aims to lower the harmful huntingtin protein in HD while keeping the healthy version. It works by blocking the step where the faulty gene gets turned into protein, stopping the problem at its source. This treatment is still in early lab testing.
GeneTAC
Design Therapeutics: Design Therapeutics is developing a small molecule called GeneTAC™ to lower mutant huntingtin (mHTT) levels in HD. One end of the molecule finds the faulty CAG repeat in the gene, while the other brings in proteins that slow gene activity. In early studies, it reduced mHTT by over 50% in mouse brain. The drug is taken by mouth and is still in preclinical testing.
Iris Medicine
Iris Medicine: Iris Medicine is developing a new kind of RNA-based therapy for HD called sbRNA (small binding RNA). This therapy is designed to reduce the production of the harmful huntingtin protein while preserving the normal version. The treatment is currently in early development.
BrainStorm
BrainStorm: BrainStorm is exploring a stem cell therapy for HD that uses a patient's own bone marrow stem cells, which are modified in the lab to release protective substances that support brain cell health. The modified cells are then injected into the spinal fluid. This approach is currently in early research stages for HD.
MitoRx Therapeutics
MitoRx Therapeutics: MitoRx Therapeutics is developing an oral drug that aims to restore the health of mitochondria (the energy-producing parts of brain cells) by boosting a natural process called sulfide signaling, which supports cell energy and protection. The treatment is currently in early-stage research.
ProMIS Neurosciences
ProMIS Neurosciences: ProMIS Neurosciences is developing an antibody therapy for HD that targets a protein called RACK1, which can misfold and contribute to disease progression. By focusing on the misfolded form of RACK1, the therapy aims to prevent harmful protein clumps in brain cells without affecting the normal version of the protein. This treatment is currently in the early stages of research.
Trailhead Biosystems
Trailhead Biosystems: Trailhead Biosystems is developing a stem cell therapy for HD using mesenchymal stem cells (MSCs). These cells have the potential to replace or support damaged brain cells affected by HD. This therapy is currently in the preclinical research stage.
FDA Approval
Production terminated
Further development uncertain
