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 usually healthy controls) 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 working 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
Xenazine/ tetrabenazine
Treats the involuntary movements (chorea) of HD by decreasing dopamine levels. It was the first HD drug to be approved by the FDA.
Austedo/ deutetrabenezine
An oral medication that treats chorea by blocking VMAT2, a protein that helps store and release dopamine. It requires less dosing than its predecessor drug.
Ingrezza/ valbenezine
Like Ausedo, Ingezza is an oral medication that treats chorea by blocking VMAT2, a protein that helps store and release dopamine.
Cellavita HD
Stem cell therapy that uses cells from the soft tissue inside teeth. These cells may help repair brain damage and reduce inflammation in HD.
Tominersen
Lowers huntingtin protein by targeting its genetic message (HTT mRNA) for breakdown. It’s delivered directly into the spinal fluid by lumbar puncture.
Votoplam (formerly PTC-518)
Oral drug that lowers huntingtin protein by changing how the HTT gene’s message is processed, leading to its breakdown.
SKY-0515
An oral “RNA splicing” drug that aims to lower huntingtin protein by altering the HTT gene’s message.
MBF-015
An oral drug that reduces dopamine release by blocking VMAT2, helping to control involuntary movements (chorea) in HD.
SOM3355
An oral drug that reduces dopamine release by blocking VMAT2, helping to control involuntary movements (chorea) in HD.
Nicotinamide Riboside (NR)
A form of vitamin B3 which helps boost levels of NAD+, a molecule essential for cell energy and repair, which is often depleted in HD.
N-Acetyl Cysteine (NAC)
An antioxidant being tested to help protect brain cells in people with early signs of HD.
WVE-003
An allele-specific antisense oligonucle- otide (ASO) designed to selectively lower mutant huntingtin (mHTT) protein by targeting a genetic variant found only on the mutant copy of the gene.
AMT-130
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.
VO659
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.
SPK-10001
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.
ALN-HTT02
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.
LPM3770164 / LY03015
A new oral drug being tested to treat HD and tardive dyskinesia (TD). It lowers dopamine activity in the brain to reduce involuntary movements and activates Sigma-1 Receptor — a protein which may protect brain cells.
ER2001
An experimental intravenous infusion that uses a specially engineered genetic package to deliver huntingtin-lowering instructions directly to brain cells.
ATL-101
A new experimental therapy administered by spinal injection 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.
Gene Therapy Reducing MSH3
Latus Bio is developing a one-time gene therapy for HD that aims to slow the disease by reducing MSH3, a protein which contributes to harmful genetic changes over time. The treatment uses an engineered viral delivery system to reach the right brain cells, while avoiding unwanted effects in other tissues.
HX127
An oral drug in development that targets a brain enzyme to restore healthy transport of BDNF, a protein that supports brain cell health.
ASO Increasing Levels of FAN1
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.
Oral Drug Reducing MSH3 Levels
LoQus23 is developing an oral drug that lowers levels of MSH3, a protein linked to harmful DNA changes that drive HD progression.
SRP-1005
An RNA-based therapy that uses the TRiMTM (Targeted RNAi Molecule) platform to deliver small RNA drugs directly to brain tissue, reducing production of the toxic huntingtin protein in HD.
Antibody Therapy Binding to mHTT
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 HD.
CRISPR-Based Gene Editing Targets mHTT
Incisive Genetics is developing a CRISPR-based gene editing therapy that aims to target the mutant huntingtin (mHTT) gene. The goal is to reduce harmful protein production without affecting the healthy gene.
LETI-101
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.
Oral Small Molecule Targeting the Huntingtin Gene and PMS1
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.
Small-Molecule Drug that Removes Harmful Huntingtin Protein
Origami is developing a small-molecule drug that helps remove the harmful form of the huntingtin protein using patient- derived brain cells.
Gene Therapy Reduces Huntingtin Protein
Passage Bio with GEMMA Biotherapeutics is developing a gene therapy for HD using a harmless virus to deliver genetic instructions directly to brain cells that aims to reduce the production of the harmful huntingtin protein.
VTx-003
A one-time viral delivery gene therapy for HD 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.
INT41
An experimental gene therapy for HD that uses a harmless virus to deliver an intrabody — a specialized antibody fragment — directly into brain cells. This intrabody binds to and neutralizes toxic fragments of the mutant huntingtin protein. INTT41 has received Orphan Drug Designation from the FDA.
Arivinas’ PROTAC® Treatment for HD
An oral treatment for HD using Arivinas’ PROTAC® technology, eliminating the harmful mutant huntingtin protein (mHTT) while preserving the normal version essential for brain health.
Oral Drug for HD That Targets MSH3
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, harmful changes may be slowed.
Oral Drug Aims to Lower the Harmful Huntingtin Protein
Anima Biotech with Takeda Life Sciences 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.
GeneTACTM
Design Therapeutics is developing a small molecule called GeneTACTM 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.
RNA-Based Therapy Reduces Harmful Huntingtin Protein
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.
Stem Cell Therapy Using a Patient’s Own Bone Marrow Stem Cells
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.
Sulfide Signaling Restores the Health of Mitochondria
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.
Antibody Therapy for HD That Targets RACK1 Protein
ProMIS Neurosciences is developing an antibody therapy for HD that targets a protein called RACK1. This therapy aims to prevent harmful protein clumps in brain cells and restore normal protein function.
Mesenchymal Stem Cells Therapy
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.
FDA Approval
Did Not Meet End Points
Further Development Uncertain
