VMAT2 Inhibitors for Chorea Can Improve Quality of Life in Huntington’s Disease

Erin Furr-Stimming, MD, Professor, Director, HDSA Center of Excellence, McGovern Medical School, The University of Texas, Houston, Texas, discussed quality of life outcomes for patients with chorea in Huntington’s disease, and the importance of utilizing available FDA-approved treatments, during a presentation at Neurology Week.

Dr Furr-Stimming began with an overview of Huntington’s disease and diagnosis. The inherited neurodegenerative disease features motor, psychiatric, and cognitive symptoms.

While DNA mismatch repair proteins are a new therapeutic target for treatment of Huntington’s disease, the presentation at Neurology Week focused on identifying chorea as a feature in Huntington’s, and treating it to improve quality of life for patients.

Chorea, a symptom of Huntington’s disease, can be identified by random, quick, involuntary movements that can be voluntarily suppressed. These may appear to flow from one part of the body to another.

To assess severity of chorea and as a way to monitor disease progression, a patient’s body regions are ranked 0-4 on the Unified Huntington’s Disease Rating Scale (UHDRS) subscale for chorea. Chorea usually increases in severity over time and appears to peak about a decade after symptom onset.

For patients, the impact on quality of life can be severe. Chorea in lower extremities can change a patient’s gait, coordination, and ability to do everyday tasks such as sitting down at a computer, walking or bending over to load a dishwasher. Instability, falls or near falls, and dropping items may become common and also negatively impact a patient’s quality of life.  

The primary goal of treatment for chorea in Huntington’s disease is to optimize quality of life. Treatment should be prioritized by how burdensome symptoms are on the patient and caregivers.

Dr Furr-Stimming provided a decision-making tree in a flow-chart attendees could follow to help guide approaches to treatment and management of Huntington’s disease.

There are two FDA-approved treatments for chorea, tetrabenazine and deutrabenazine, Dr Furr-Stimming highlighted, noting additional medications are available for motor and nonmotor symptoms.

Tetrabenazine and deutrabenazine are both VMAT2 inhibitors that showed meaningful clinical benefit to reduce patient’s UHDRS chorea subscale score. Furthermore, valbenazine, which has been approved for treatment of tardive dyskinesia, is under investigation in the late-stage phase III KINECT-HD trial for treatment of chorea in Huntington’s disease (but is not currently FDA-approved).

Despite available treatments, there remains an unmet medical need for treatment of chorea, Dr Furr-Stemming called out.

Data from an Enroll-HD analysis Dr Furr-Stemming is an investigator on shows less than 25% of patients with Huntington’s disease and manifest chorea receive treatment for chorea.

Strategies and medications to help manage the disease exist. Dr Furr-Stimming stressed early diagnosis and management of chorea is important to improving quality of life outcomes for patients with Huntington’s disease. —Kaitlyn Manasterski

Furr-Stimming, E. Hope for Chorea Control in Huntington’s Disease: A Focus on Differential Diagnosis and VMAT2 Inhibitors for Treatment. Presented at Neurology Week 2021; July 14-18. Virtual.