uniQure, a leading gene therapy company, recently shared an update on a Phase 1/2 clinical study evaluating AMT-130 for Huntington’s disease. The safety and proof-of-concept study enrolled 26 participants with early-manifest Huntington’s disease; this means that those affected are still in the early stages of their disease and still largely functional. Participants were split into two cohorts, with 10 in the low-dose cohort and 16 in the high-dose cohort; 10 patients between these two groups received a placebo, while the remaining received AMT-130. 

What Does the Data Say? 

AMT-130 is an investigational gene therapy that, as uniQure explains: 

consists of an AAV5 vector carrying an artificial micro-RNA specifically tailored to silence the huntingtin gene, leveraging our proprietary miQURE™ silencing technology. The therapeutic goal is to inhibit the production of the mutant protein (mHTT).

The results of the study found that AMT-130 offered benefits to patient health, shares Neurology Live. Patients were treated for one year, followed by a 5-year follow-up period. Findings from the study show that:

• Functional ability was preserved in treated individuals when compared to non-treated individuals. Those taking a low-dose of AMT-130 had sustained motor and functional benefits for a longer period of time than those receiving a high dose. 
• People who received the placebo saw reductions in function and motor skills. 
• Mean total brain volume decreased across all three groups. People who received the lower dose of AMT-130 also saw lower mutant huntingtin protein in their cerebrospinal fluid. Interestingly, those receiving the high dose saw a significant increase in mutant huntingtin protein. 
• AMT-130 was found to be safe and relatively well-tolerated. More serious adverse events included back pain, central nervous system (CNS) inflammation, and severe headache; these were all seen in people receiving the higher dose. 

While there are differences in the findings based on dose, the Data Safety Monitoring Board found that both the high and low doses of AMT-130 were safe for further development. Moving forward, both doses will be evaluated in clinical studies in conjunction with immunosuppressive therapies. 

About Huntington’s Disease (HD)

Huntington’s disease is a progressive neurodegenerative disease that results when abnormally long, toxic chains of huntingtin protein build up. These long protein chains are caused by HDD gene mutations and bind themselves to neurons. Neurons are nerve cells. They’re found throughout your brain and central nervous system, and they’re responsible for sending signals to different parts of your body. But these protein chains cause neurons to die, interrupting these signals. People often begin experiencing Huntington’s disease symptoms in their 30s or 40s. The prognosis is currently around 15-20 years following diagnosis. There is no cure for Huntington’s disease and treatments are focused on managing symptoms. Therefore, there is a huge unmet need within this community.

Signs and symptoms of Huntington’s disease may include difficulty swallowing, an unsteady gait, issues with balance and coordination, cognitive decline, memory issues and forgetfulness, involuntary movements, and changes in mood, behavior, or personality.