Huntington’s disease (HD) is a genetic disorder caused by a gene variant or mutation in a person's huntingtin gene. The disease leads to a breakdown of nerve cells in the brain, affecting the individual’s ability to move, their mood, and how they think. Learn how gene therapy could slow or stop the progression of this disease, along with helpful information on clinical trials, and resources to stay informed on the research landscape.
About Huntington’s Disease
Cause of Disease - Huntington’s disease is caused by a gene variant, also known as a gene mutation, in the huntingtin (HTT) gene. This change, which appears as an expanded or repeated gene, creates too much of the huntingtin protein, which is damaging to the brain and body. This causes a progressive breakdown of neurons, the main cell type in our nervous system. Neurons in the brain send messages back and forth from our brain to other areas of the body. As toxic levels of huntingtin protein causes damage to neurons, individuals with the disease face many symptoms that include changes in movement, mood, and memory.
Symptoms - Symptoms of HD typically appear between the ages of 30 and 50 and worsen over a period of 10 to 25 years. The disease currently has no cure, but there are approved treatments and interventions that can help to manage HD symptoms. Learn more about genetic testing and family planning below.
Gene Therapy Approaches
The gene therapy approach aims to limit the production of the toxic huntingtin protein leading to a slower breakdown of neurons. Gene therapies are being explored in two approaches to treat Huntington’s. The first approach attempts to reduce the amount of Huntington protein produced in the brain and body to slow or stop progression of HD. The second approach uses genetic material to ramp up expression of genes whose functions decline or are damaged over the course of HD to boost the brain and body’s natural resilience against the progression of HD.
The gene with its new instructions can be delivered to the cells using a viral vector. Viruses can be used as vectors because they have evolved to be very good at getting into cells. Scientists have learned how to remove the viral genes and use this same ability to treat or prevent disease. There are a few ways vectors may deliver genetic material to target HD:
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Gene therapy introduces the new genetic material to block or slow the HTT gene from creating the toxic protein. This aims to be delivered one time.
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RNA therapy, a type of gene therapy, utilizes microRNA. RNA is a template to make proteins that are copied from the genetic blueprints of DNA. This means that RNA translates a gene’s genetic information, instructing a cell how to create a protein or enzyme. With this in mind, RNA could then also change how a gene expresses itself. MicroRNAs do not encode information to help cells make proteins. Rather, they help regulate existing RNAs that do create proteins. With gene therapy, a vector would deliver microRNAs into the cell, helping to limit the cell’s production of the toxic HTT protein. This aims to be delivered one time.
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Antisense oligonucleotide therapy blocks or alters how cells express specific genes. Synthetic DNA or RNA strands known as antisense oligonucleotides—or ASOs—would be delivered to the cells. The ASOs then bind to a gene and block its ability to produce the protein. There are many different ways to deliver ASOs into the cells. In some cases, it is a vector delivery system, and in other instances, no carrier is needed. These typically require repeated doses to maintain a therapeutic effect.
Learn more about gene silencing, mircoRNA therapies, and ASO therapies in Gene Therapy Approaches.
Treatment Pipeline
While there are treatments to help manage the disease symptoms, there are currently no cures or disease modifying treatment options for Huntington’s Disease, but gene therapy is being investigated in clinical trials and preclinical studies.
Clinical trials are a required part of the research process that aims to understand the way a drug or treatment will interact with the human body and whether it is safe and effective. Preclinical studies are an even earlier stage of research to confirm the safety and effectiveness of a treatment in animal or cell-based models before proceeding with a human clinical trial. Clinical trials may differ on various aspects of their design. Speak with a trusted provider or member of the clinical trial research team if you are considering participating in a clinical trial.
To stay up to date on active and recruiting clinical trials in the U.S. or globally, visit the ASGCT Clinical Trials Finder. To learn about clinical trials specific to Huntington’s disease, visit HDTrialfinder.org.
Participating in a Clinical Trial
It is important to be well-informed when deciding to participate in a clinical trial. Below are some key points to consider. Visit the Considering a Clinical Trial page for more information and resources to help guide you.
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Eligibility - Eligibility for a trial is based on strict inclusion and exclusion criteria. These are specific factors that determine whether a person can or cannot enroll in a clinical trial. This is an important way for researchers to understand if the gene therapy is working properly and to ensure participant safety. These criteria may include factors such as age, physical ability, medical history, and more. Speak with a healthcare provider or a member of the clinical trial research team to help determine if you or your child may be eligible for a clinical trial.
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Risks - As with any medical intervention, there are risks that need to be carefully considered. Before participating in a clinical trial, a member of the research team should review any potential risks and benefits with the patient or caregiver. Therapies being studied in clinical trials are not a guaranteed cure and cannot guarantee beneficial results. There is always a chance that the investigational treatment may not work. In the event a person is not satisfied with the outcome, the person may not be able to receive another dose of the gene therapy. In addition, participating in a clinical trial may prevent future participation in other trials or from receiving other types of treatments. Gene therapy can be an alteration for the lifetime, so people should be aware that there could be long term effects (both good or bad) that are not known at this time.
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Benefits - Participating in a trial may offer many potential benefits compared to not receiving any form of intervention for a fatal disease. Gene therapy aims to be a one-time treatment with lasting positive effects that slow or stop disease progression for a lifetime. However, there is no guarantee. If gene therapy is received earlier in the course of disease, it has the potential to stop damage before it occurs.
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Long-term follow up - It is the patient’s responsibility to comply with the long-term follow-up of a trial. The Food and Drug Administration (FDA) guidelines require the clinical trial research team to monitor safety and potential long-term effects of a gene therapy. Follow-up may require in-person appointments that vary in frequency and location, or completion of mailed packets with response forms. The need for long-term data collection for a gene therapy trial can last up to 15 years—another reason to consider all outcomes and responsibilities that come with committing to a clinical trial. There are a limited number of participants in trials so a lack of attendance at follow-up appointments leads to not enough study data. This could negatively affect FDA approval of a new therapy and thereby limit access to the therapy by patients who did not participate in the clinical trial.
Genetic Testing
If a child has at least one parent affected by Huntington’s disease, there is a 50-50 chance that they will inherit the gene variant or mutation that causes the disease. If at-risk individuals want to be tested, the Huntington’s Disease Society of America recommends having it done at a genetic testing center that follows the HDSA guidelines. Testing procedures at these centers involve sessions with professionals knowledgeable about the disease, along with local services to connect with. These include patient organizations that work to lower stigma, promote research engagement, and provide educational resources.
Family Planning
Genetic testing also has implications for family planning. Even if a potential parent does not currently show symptoms of the disease, there is a risk that they may pass it along to their children or may show symptoms themselves later in life. Genetic testing could identify whether a person has the Huntington’s gene to help during family planning.
Visit HDSA’s website to find approved services, providers, and resources in your area.
Access
At this time, we do not know if or when gene therapies will be approved by the FDA and commercially available for people living with Huntington’s disease. The overall process may take several more years, until it is deemed safe and effective by the FDA.
Stay Informed
A number of organizations provide individuals with Huntington’s disease and their families, with resources, research updates, and support: