Novel Therapy May Improve Chorea Symptoms in Huntington’s Disease

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The drug has a similar mechanism of action as tetrabenazine, but a different pharmacokinetic profile.

Deutetrabenazine may help reduce chorea in Huntington’s disease, according to results from a small, placebo-controlled study.

Results, published in JAMA, indicate that treatment with deutetrabenazine also improved measures of impression of change and physical functioning, in addition to chorea score.

The symptom, which is prominent in the neurodegenerative disorder, can interfere with daily functioning and increase the risk of injury. Currently, tetrabenazine (Xenazine®) is the only FDA-approved treatment for chorea associated with Huntington’s, however the frequency of dosing and associated neuropsychiatric symptoms makes it a less than ideal therapy in this patient population.

In order to assess the efficacy and safety of deutetrabenazine, Samuel Frank, MD, of Harvard Medical School in Boston, and colleagues enrolled 90 ambulatory adults with Huntington’s (mean age, 53.7 years; 40 women [44.4%]) with a baseline chorea score of 8 or higher in a randomized, placebo-controlled, double-blind study. Patients were randomized to receive either deutetrabenazine (n=45) or placebo (n=45), which was titrated to optimal dose over 8 weeks and maintained for 4 weeks followed by a 1-week washout period.

Overall, mean total maximal chorea scores improved from 12.1(95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9) in the treatment group compared with 13.2 (95%CI, 12.2-14.3) to 11.3 (95%CI, 10.0-12.5) in the placebo group, with a mean between-group difference of -2.5 (95% CI, –3.7 to –1.3) (P< .001). Fifty-one percent of patients in the treatment group (n=23) deemed the treatment successful compared to 20% of the placebo group, as measured by the Patient Global Impression of Change (PGIC) (P=.002). Based on the Clinical Global Impression of Change, treatment success was achieved in 42% of the treatment group vs 13% of the placebo group (P= .002).

Less prominent changes were observed for the 36-Item Short Form– physical functioning subscale score (SF-36), in which scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5) in the treatment group compared to 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6) in the placebo group, for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P= .03). No difference between groups was observed for the Berg Balance Test. The authors noted that adverse events were similar in both groups, with some patients experiencing depression, anxiety, and akathisia.

Overall, the use of deutetrabenazine was associated with improvements in motor symptoms at 12 weeks.

“The difference in total maximal chorea score associated with deutetrabenazine treatment that was observed in this study is notable given the progressive decline in total maximal chorea score and total motor score that has been previously described as part of the natural history of Huntington disease,” the authors wrote, noting that further investigation is needed to determine the long-term efficacy and safety of the drug.


Frank S, Testa CM, Stamler D, et al. Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease: A Randomized Clinical Trial. JAMA. 2016; doi:10.1001/jama.2016.8655.