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Huntington’s Disease FAQs
Answering Your Questions: Huntington’s Disease Treatment

Released: November 20, 2023

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In October 2023, Victor W. Sung, MD, presented at a session titled “The Changing Landscape of Huntington's Disease Treatment” at the CCO Hot Topics in Neurology summit. During this session, Dr Sung shared valuable information about improving management of Huntington’s disease (HD) and assessing the efficacy and safety of new agents available for patients. Here, he provides answers to audience questions that were asked during the session.

Is  HD seen in children, adolescents, and young adults?  
Yes, HD can be seen among people in their late teens and early 20s; this is called juvenile-onset HD (JHD). Overall, JHD represents approximately 5% to 10% of all persons living with HD . It is defined by an onset age younger than 20 years   and will almost always be accompanied by a CAG repeat length >50 . For those who are diagnosed at a younger age, their disease is expected to progress faster, as CAG repeat lengths increase .

In addition, the disease phenotype for JHD is different, with one of the biggest differences being that patients generally experience less chorea and more parkinsonism  than their older counterparts. So, if you see a child with parkinsonism, you should think of JHD. I find that if patients’ onset is in their late teens or early 20s, they may have strongly mixed HD presentation with both chorea and parkinsonism. 

Does the initial presentation of chorea vs other HD symptoms determine length or speed of disease progression?
I do not think so. There is no evidence that CAG repeat length or other social or environmental factors determine why somebody will present more or less with chorea or other motor-related symptoms. It is a bit more complicated than this. We know that certain groups, like those with late-onset HD, tend to have a motor predominance in their phenotype . Both genetics and now epigenetics are what really complicates things and tend to predict the speed of disease progression .

How do you approach patient and caregiver discussions regarding treatment initiation for chorea, given the lack of insight that some may have?
Great question. I really view it as we are the care providers. Especially given the lack of insight, it is our job to point things out to patients when they are not able to notice it themselves. When patients say chorea does not bother them and I know we have already talked about it, I will make sure they understand that chorea involves involuntary movements that affect their voluntary movements. This impact, if it has a functional impact in their lives, then tends to bother them.

Do you treat younger patients with the same doses and titration schedules as your older patients? At what age do you start considering changing your treatment approach?
We generally advocate in all of neurology to treat patients with the dose required to control their symptoms. That is what you should be focusing on as a provider. If patients’ symptoms are controlled at a low dose, stay there. If it takes a higher dose to control the symptoms, then go there. As far as speed of titration, I generally follow the same weekly titration provided in most agents’ prescribing information.

How would you approach patients who want to treat both their chorea and depression?
VMAT2 inhibitors have a black box warning regarding their use in depression. The tetrabenazine boxed warning is based on actual data  . In the clinical trial for patients receiving tetrabenazine, approximately 20% experienced depression. In addition, 1 patient completed suicide and another had suicidal ideation on the treatment arm . The black box warnings for valbenazine and deutetrabenazine for depression are class effects. The incidence here is much less , as neither agent caused significantly worsened depression among treated patients in their respective study.

So, if I want to use a VMAT2 inhibitor in those with depression, I address the black box warning head-on by educating patients. I tell them that these agents have a warning related to worsening depression and suicidal ideation and that these symptoms are also common in HD. I tell them: “Regardless of whether I put you on this VMAT2 inhibitor or any other medicine, I care about depression and suicidal ideation because it comes from your disease. So, if your depression worsens or you start to develop suicidal ideation, I need you to contact me right away and let me address it.”

What is the impact of VMAT2 inhibitors on patients’ cognition, behavior, and mortality?
The data show that VMAT2 inhibitors treat only chorea and motor symptoms . There is no statistically significant impact on cognition or behavioral symptoms. For mortality, this raises an interesting question. There is a higher rate of mortality in patients taking VMAT2 inhibitors  compared with those not taking these agents. If you look at patients with HD and chorea, their mortality is higher than patients with HD without chorea . That adjusted mortality actually goes down a little bit, or so we think it does, once patients are treated. But overall, those taking VMAT2 inhibitors vs those who are not see a mortality that is a little bit higher because they have symptomatic disease. It is not thought that there is a causal link to worsening of mortality.

Your Thoughts?
Are you comfortable prescribing any of the novel VMAT2 inhibitors for the management of chorea in HD? What additional questions do you have on this topic? Answer the polling question and let us know by posting a comment.

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