Huntington’s disease is a genetic neurodegenerative disease that can have a devastating effect on a patient – physically, psychologically, and cognitively. Chorea is the most pronounced symptom, but a slew of mental health and cognitive problems have a major impact, both on the patients and their caregivers and families.

Recently, Rare Disease Report spoke with Burton Scott, MD, PhD of Duke University about this disease and some of the recent work regarding it in which he is involved, including a recent Phase 3 study published in the Journal of the American Medical Association (JAMA) Neurology.

RDR: Can you provide a brief overview of Huntington’s disease?
Scott: Huntington’s disease is caused by a genetic mutation that’s interfering with the functioning of a protein called Huntingtin that seems to have an effect on the metabolism in the brain and that causes progressive difficulty and inexorable decline in motor function, behavior and cognition.

We have medicines that are helping with some of the symptoms and signs of Huntington’s disease, particularly motor findings but there’s a lot of work that’s being done trying to come up with better treatments that may have some impact on progression and perhaps even turn off the gene that’s causing the problem in the first place.

RDR: How does it impact the family?
Scott: It’s an illness that certainly depletes family resources because folks are growing up watching their family members die from this. People can’t work. The disease occurs during a person’s main years of earning capacity. Often times, the disease is new to the family but more commonly, families have become used to seeing various members of their of their family develop the illness and decline.

There’s a lot of hope for gene treatments or treatments that might turn off the Huntington’s gene using inhibitory RNA.

RDR: How does tetrabenazine help HD patients?
Scott: Tetrabenazine is a drug that reduces the amount of the neurotransmitter dopamine in the brain that’s available for interaction with receptors. Basically if you reduce dopamine in the brain of Huntington’s patient you reduce their abnormal movements – sort of the opposite effect in another brain illness, Parkinson’s disease, where those folks don’t have enough dopamine. Chorea is associated with too much dopamine so tetrabenazine is a drug that basically reduces the amount of dopamine available for a neurotransmission. Side effects can problematic. We have to watch out for people that are depressed who can become more depressed and even suicidal on the drug. People that take too much tetrabenazine can also slow down too much and look parkinsonian.

we’ve got the newer version of tetrabenazine, a deuterated form, deutetrabenazine, that  recently became available.

RDR: Can you describe the recent study switching patients from tetrabenazine to deutetrabenezine?
Scott: The JAMA article describes o the ability to quickly change from a regular tetrabenazine to the deuterated form and there was a small group of centers involved with taking patients that were on tetrabenazine and had reasonable control of their Korea on that drug and then switch them overnight to deutetrabenezine. It was found from the study that the patients did tolerate that overnight switch quite well and then with subsequent adjustments, they were able to get the doses that control their chorea as least at least as well as the tetrabenazine and I think overall the deutetrabenezine form was tolerated better.

I’m comfortable using either one of them as long as patient able to get the drug at a reasonable price. Both are good choices but all of the things being equal, l being able to give a drug twice a day instead of three or four times day is certainly an improvement.

RDR: Are there any other studies you are working on?
Scott: We are involved with is looking at neuroinflammation in Huntington’s disease. The SIGNAL study is targeting protein called semaphorin 4D with the working hypothesis that infusing an antibody directed against semaphorin 4D into a vein on a monthly basis will allow it to get into the brain and presumably interfere with neural inflammation in the brain and make it make a difference in the course of the illness.  That particular study involves patients with early Huntington’s disease coming in once a month to get an infusion of this antibody and that study is ongoing.

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