In the Journal of Neurology
, Benjamin Underwood and colleagues have published the results from a study that examined the safety and tolerability of the anti-hypertensive drug rilmenidine in patients with Huntington’s disease (HD).
HD, a genetic neurodegenerative disorder depicted by a combination of motor, cognitive and psychiatric problems, usually presents in adults in their 30s or 40s. In HD patients, mutations in the Huntingtin
gene lead to a mutated huntingin protein that leads to the neuronal deterioration. Current treatment options are limited, and there is no currently-approved treatment with the ability to prevent or delay disease progression.
Underwood and his team of researchers from Addenbrooke's Hospital in Cambridge, U.K. assessed the safety of rilmendine in HD patients to determine if it is safe for larger trials. The study was based on another study that exhibited rilmendine’s effectiveness in increasing the degradation of the mutant huntingtin protein and attenuation of HD-like symptoms in animal models of the disease.
In the 27-month open-label study, 18 patients with mild-to-moderate HD received rilmenidine (1.0 mg/day) for 6 months followed by a dose of 2 mg/day for an additional 18 months. The patients were further followed for 3 months during a washout period. The primary outcome measure was the number of withdrawals and serious adverse events (AEs). Of the 18 patients, 12 completed the study. Reasons for the 6 withdrawals included problems tolerating procedures (MRI, and venipuncture; n=2), depression requiring hospital admission (n=1), and logistical reasons (n=3).
At the end of the study, 3 serious AEs were recorded: depression requiring hospitalization; broken wrist following a fall; and migraine. None of the severe AEs were deemed to be drug-related.
Several secondary outcome measures examining various safety and motor functions were also taken, and the authors noted that while the study was not powered to assess HD functions, it did uncover that some aspects of the Unified Huntington’s Disease Rating Scale (UHDRS) scores were slightly improved (total functional capacity; independence scale) while others declined (motor score).
Table 1: Secondary Outcome Measures
- ED = extra-dimensional shift on the CANTAB intra-dimensional/extra-dimensional set-shifting task
- MMSE = Mini Mental State Examination
Rilmenidine appears to be relatively safe and well tolerated in patients with HD, however, whether the drug can slow down the progression of HD is unknown based on these results. The authors suggested that larger, randomized, placebo-controlled trials are still required.
Underwood BR, Green-Thompson ZW, Pugh PJ, et al. J Neurol.
Published online October 26, 2017 ahead of print. doi.org/10.1007/s00415-017-8647-0
Table courtesy of Underwood et al, an open-source publication.
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