How they work
Brain cells send signals to each other via the transfer of neurotransmitters. VMAT2 is responsible for loading neurotransmitters into small fluid-filled sacs called vesicles, which transport neurotransmitters between neurons.
VMAT2 inhibitors block this activity, which
stops the uncontrolled signaling that leads
to chorea and uncoordinated movements
in Huntington’s disease.
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VMAT2 inhibitors for Huntington’s disease
Treatment guide:
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Treatment guide:
How to take them
VMAT2 inhibitors block signaling within the brain, which can have unintended side effects. Because signaling of mood hormones like dopamine and serotonin can be disrupted, people with depression should not receive certain VMAT2 inhibitors, as they can worsen these symptoms.
Other possible side effects include drowsiness, dry mouth, insomnia, and restlessness.
Side effects
The Food and Drug Administration has approved three types of VMAT2 inhibitors for the treatment of chorea with Huntington’s disease:
tetrabenazine (Xenazine, also available as a generic)
deutetrabenazine (Austedo)
valbenazine (Ingrezza)
Valbenazine is a more selective VMAT2 inhibitor. This may limit off-target activity and reduce the side effects seen with this class of drugs.
Available options
Following FDA approval in 2008, a 2009 meta-analysis of 22 clinical trials found tetrabenazine provided better control of chorea symptoms than other options used at the time.
The FDA approved deutetrabenazine and valbenazine in 2017. About 51% of clinical trial participants for deutetrabenazine reported improvements in symptoms and daily functioning. Reports also showed that valbenazine was a well-tolerated option for improving chorea symptoms.
Effectiveness in Huntington’s disease
All VMAT2 inhibitors are taken orally as tablets or capsules. Depending on the form of the medication, people may need to take them with food. Valbenazine is also available in a capsule that people can open and sprinkle on food.
VMAT2 inhibitors are taken each day. Exact dosing may vary from person to person. Healthcare professionals may adjust the dose of the VMAT2 inhibitor based on symptoms and whether there are other health concerns.
