Research Program
As one of the world's leaders in both clinical and basic research, the Huntington's Disease Center at Johns Hopkins offers a wide range of opportunities for individuals and their families to participate in clinical research studies of Huntington's disease (HD). Participants may receive clinical testing and other services related to these studies. The National Institute of Health (NIH), the Huntington's Disease Society of America (HDSA), and the CHDI Foundation provide major funding support for the Center's on-site research programs.
Types of Studies:
- Pre-clinical Trials – these are studies that occur before human testing to determine if a new drug, medical device, or treatment is safe and effective. This is done through laboratory and animal testing. The Johns Hopkins Neurobiology Laboratory has been conducting extensive research on mice to look at various aspects of the HD genetic makeup and how it might react with certain types of therapeutic drugs.
- Observational Studies – research that is focused on observing how participants’ health, habits, or past behaviors might identify certain patterns and outcomes. Many of the observational studies that our site participates in look at how HD changes and progresses over time via data collected from interviews and surveys with participants, in addition to the collection of biosamples like blood and cerebral spinal fluid. No treatment, drug, or intervention is given to participants in these studies. Examples of Observational Studies: Enroll-HD, HDClarity, etc.
- Therapeutic Drug Trials/Clinical Trials – these are studies that are looking for a cure/treatment of a particular disease or condition. Johns Hopkins Huntington’s Disease Center is proud to partner with pharmaceutical companies that have dedicated time to finding a cure or treatment for HD. These drugs can be in the form of a daily oral medication, injection via a lumbar puncture (aka spinal tap), infusion into the blood, or brain surgery. Examples of Clinical Trials: Generation HD1, Generation HD2, AMT-130, etc.
If you are interested in participating in research at the Johns Hopkins Huntington’s Disease Center of Excellence, please email the following information to [email protected]:
- Name of the patient?
- DOB of the patient?
- Where does the patient currently live?
- Has the patient undergone genetic testing? If so, please provide their CAG repeat number (if known).
- Does the patient/family members notice any symptoms?
- If so, please describe (i.e. motor, cognitive, mood changes, etc.)
- Has the patient been told by their doctor that they are showing HD symptoms?
- If so, please describe (i.e. motor, cognitive, mood changes, etc.)
- Is the patient currently being seen at an HD clinic?
- What insurance does the patient currently have (in case a non-research visit is required)?
- Has the patient ever participated in research?
- Is the patient currently enrolled in Enroll-HD? Where?
- Can the patient tolerate MRIs?
- Can the patient tolerate blood draws?
- Has the patient had any issues in the past with spinal taps? (Most gene therapy studies will require spinal taps for safety or drug administration purposes.)
Currently Active Studies - Enrollment Open
- Enroll-HD
- HDClarity
- HD Center Research Database Study
- JHU CSF/Blood Biobanking Study
Currently Active Studies – Enrollment Closed
- Generation-HD2 (Sponsor: F. Hoffmann-La Roche Ltd.)
- AMT-130 (Sponsor: uniQure biopharma B.V.)
Upcoming Studies – Enrollment Timeline TBD
- First-in-human evaluation of novel mutant huntingtin PET radioligand [18F] CHDI-00895650 (Sponsor: CHDI)
- HTT227: A randomized, placebo-controlled, double-blind Phase 3 study to evaluate the efficacy, safety and tolerability of Votoplam in participants with Huntington’s Disease (Sponsor: Novartis Pharmaceuticals)
Completed Trials
- SAGE-718 Perspective Program (Sponsor: Sage Therapeutics, Inc.)
- Dimension 718-CIH-201
- Surveyor 718-CIH-202
- Purview 718-CIH-301
- PROOF-HD (Sponsor: Prilenia Therapeutics)
- Generation-HD1 (Sponsor: F. Hoffmann-La Roche Ltd.)
- Gen-Extend (Sponsor: F. Hoffmann-La Roche Ltd.)
- SIGNAL-HD (Sponsor: Huntington Study Group)
Genetic Studies
Hopkins researchers have been recognized as leaders in the fields of Huntington's disease (HD) gene discovery and genetic testing. Recent advances have expanded the clinician's ability to provide more exact information about age of onset and other factors important to families dealing with HD.
Currently, we are searching for the factors that influence how fast HD progresses. The length of the CAG repeat in the huntingtin gene is one major predictor of age of onset. However, we have evidence of other familial factors that are likely genetic contributions to age of onset as well. We and other centers have found that the length of the CAG repeat does not predict the rate of progression, and we are searching to see if familial factors might be involved in this as well.
We are also very interested in finding other genes, which can cause HD-like diseases. The research program, run by Dr. Russell L. Margolis, has identified several such genes, including HDL-2, DRPLA, and SCA-12. Patients with HD-like syndromes but who do not have the HD gene mutation are of great interest for our research programs.
Testing for these studies is performed by the Neurogenetic Testing Laboratory with The Baltimore Huntington's Disease Center.
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A: Symptomatic treatments reduce specific symptoms such chorea or depression. They do not change the underlying course of the disease. And they may take effect quite rapidly. For example, tetrabenazine and its derivatives begin to work for chorea almost immediately. But they also lose their effectiveness when the medication is stopped. Disease-modifying treatments would actually alter the underlying progression of degeneration in the brain. Thus their effectiveness might take many months to be evident, but would be long-lasting.
A more familiar example of these distinctions might be bronchitis from a bacterial infection. Symptomatic treatments like cough suppressants would work quite quickly (minutes to hours), but would not change the course of the illness. By contrast, an antibiotic (targeted at the correct infectious organism) might take several days to work, but would cure the underlying infection.
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A: There are none so far. That’s what makes finding disease-modifying treatments the key task in HD research.
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A: The mutant HD gene Huntingtin (i.e. the expanded CAG repeat) codes for a mutant Huntingtin protein, via an intermediary information-carrying molecule called messenger RNA. The mutant Huntingtin protein is believed to be the major cause of damage within neurons, leading to neurodegeneration within the striatum and other areas of the brain. New molecular biology techniques make it possible to attempt to interfere with the function of the messenger RNA molecule leading to a reduction in the levels of the mutant Huntingtin, and thus a decrease in the amount of neurodegeneration. This would, for the first time, actually modify the course of the disease. Ultimately the symptoms would be reduced as well. This overall approach is often called ‘RNA-interference’ since it interferes with the function of the messenger RNA, thus achieving ‘Huntingtin-lowering’ (or if very highly effective, ‘Huntingtin-silencing’). There are a variety of strategies being pursued to achieve this goal. Two of the major ones involve ‘antisense oligonucleotides’ or ‘viral vectors’.
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A: They are DNA molecules specially designed to target the Huntingtin messenger RNA and cause its degradation, thus achieving Huntingtin-lowering and disease-modifying therapeutics. Because they are large molecules, they do not cross the barrier around the brain so they cannot be taken by mouth or even by intravenous injection. They could be injected directly into the brain (as was done in animal studies) but the more typical strategy is to inject them via a small needle into the lower back into the fluid that surrounds the brain and spinal cord known as the cerebrospinal fluid. This is called ‘intrathecal administration’.
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A: HDClarity is a research study currently underway here at Hopkins in which cerebrospinal fluid (CSF) is collected to study the progression of HD using a routine procedure called a lumbar puncture or spinal tap, which takes about 30 minutes. The goal is to quantify levels of mutant Huntingtin and other biomarkers. A biomarker is anything that can be measured, such as chemical substances in the CSF that reflect neuronal injury, in order to help us understand HD.
Biomarkers may help guide future research studies and clinical trials, as well as help us better understand who will most likely benefit from a particular treatment. CSF can be used to provide information about the brain and nervous system that is impossible to obtain in any other way. Individuals with a positive or negative HD genetic test status, or family not related through blood (i.e. spouses and partners) may participate.
We are actively enrolling for the HDClarity study, and were the first US site (and as of December 2017 the only U.S. site actively enrolling). Participants must be part of the ongoing observational study, called ENROLL-HD, which just involves tracking routing motor, cognitive and emotional changes over time.