- Huntington’s disease is a genetic brain disorder that causes symptoms like uncontrolled movement and decline in thinking skills.
- Treatment often focuses on symptom relief, but experts are seeking more effective interventions.
- Recent findings of a drug trial tested an effective gene therapy that slows down the progression of Huntington’s disease by 75% compared to not receiving the therapy.
Huntington’s disease occurs because of a defective gene. It’s a condition that gets worse over time, and there is currently no cure. Thus, one area of research involves seeking out treatments for the condition. According to University College London (UCL), researchers may have developed a possible treatment to slow down Huntington’s disease that is effective over three years of treatment.
Although the research has not yet been published in a peer-reviewed journal, it offers hope: The treatment, AMT-130, helped to slow progression by 75% at the greatest dose.
This research was a phase one and two clinical trial involving 29 individuals with Huntington’s disease who were compared to a control group. This control was an external cohort that was part of a long-term study called Enroll-HD, which tracks the progression of Huntington’s disease.
The intervention group received a gene therapy called AMT-130, developed by the company uniQure.
Twelve of the 29 participants received a high dose of the gene therapy and had three years of follow-up data. These participants with the three-year follow-up who got the high dose had a slowed disease progression that was 75% less than the progression in the control group. Researchers found significantly better scores on evaluations of disease progression.
They also found lower levels of a protein in the spinal fluid among intervention participants. When this protein is found in spinal fluid, it indicates nerve damage. The amounts they found were lower than the amounts these participants had at the beginning of the study, overall indicating that the nerve damage had slowed down.
The research also indicates that AMT-130 was safe and that participants tolerated it well. AMT-130 is given in a surgery via a one-time injection into a specific area of the brain.
Anne Rosser, PhD, Professor of Clinical Neurosciences, who was the site principal investigator for Cardiff, the coordinating principal investigator for the study set up in the U.K., and consultant to UniQure, highlighted the following about the research to Medical News Today:
“The results are highly significant and suggest that this therapeutic has slowed the disease progression in HD over a three-year period. This is in a small number of patients, and the comparison was with a large number of patients in an observational trial who didn’t receive the study drug, which means that further data collection on the therapeutic will almost certainly be required. However, it provides important proof-of-concept that Huntington’s is modifiable and a lot of hope that the UniQure product may eventually be prescribable as a therapy in this disease.”
The biggest limitation to this research is that the related study hasn’t actually been published yet, and the research is not totally complete. Rosser explained that “the study is ongoing in that the sponsor is still undertaking a small number of surgeries in the U.S., [t]he results are not yet peer-reviewed or published, so this will need to happen.”
Additionally, since this research only examined three years of follow-up, it’s unclear if the effects last beyond this timeframe. Future research can look into even more long-term results.
The intervention was also only used in a small number of participants, so work in larger groups will also be important. An even smaller number of participants received the AMT-130 at a high dose, so follow-up on dosing amount may also be helpful.
Because of the research done in the U.K., it’s possible that work in other groups and countries will also be required. It’s unclear what uniQure’s role as a company was in this clinical trial, but depending on the situation, it could introduce bias into the results.
Rosser noted that an area of research that will also need to be addressed is the administration of AMT-130.
“Another challenge is how to achieve widespread dissemination of the therapeutic, as it needs to be delivered directly to the brain through a neurosurgical procedure. Currently, this takes around 12 to 18 hours, so it will be necessary to work on the best ways to make this surgery faster, more efficient, and eventually suitable for delivery more routinely.”
This finding is a significant leap toward a potential treatment for Huntington’s disease. The development of this treatment could lead to drastic changes related to Huntington’s disease in the future.
Kan Cao, Ph.D., a Professor and Vice Chair in the Department of Cell Biology and Molecular Genetics at the University of Maryland, College Park, who was not involved in the research, noted the following regarding how this might impact people with Huntington’s disease:
“This is, so far, the first therapeutic in HD [Huntington’s disease] to show a durable disease-modifying effect in humans (i.e., beyond symptomatic relief)…If these findings hold up in larger, more controlled trials, the implications are broad and profound: Disease modification becomes feasible.”
— Kan Cao, PhD
“[Huntington’s] could shift from ‘untreatable degenerative disease’ to one where slowing or halting progression is clinically achievable. This would reshape prognosis, patient counseling, care planning, and therapeutic development. If safety is demonstrated, future trials may enroll premanifest (carriers) or early-stage individuals, potentially delaying onset or significantly delaying disability,” Cao added.
Of course, it will take time to get the treatment available to people with Huntington’s disease, but work is underway to get the treatment approved for clinical use.
“The therapeutic is not yet available to prescribe, and this will take some time — the Trial sponsor (uniQure) plans to apply to get approval to market the drug. They plan to submit an application to the U.S. Food and Drug Administration early next year, requesting accelerated approval in the U.S., with applications in the U.K. and Europe to follow. We don’t know yet whether the regulatory agencies will require further trial work or what that might be,” Rosser said.
