According to results of the phase 3 MermaiHD trial published Online First in The Lancet Neurology, a unique drug (pridopidine) that stabilizes dopamine signaling in areas of the brain controlling movement and coordination in patients with Huntington's disease (HD), a condition characterized by an imbalance in the signaling chemical dopamine, seems to be well tolerated and merits further investigation.
So far, no medication has demonstrated the ability to improve the loss of the ability to move muscles voluntarily. At present, the only medication approved for Huntington's disease is tetrabenazine. However, this drug only treats chorea (an abnormal involuntary movement disorder) and is connected with serious adverse effects.
Pridopidine is part of a novel class of medications known as dopidines. Dopidines act as dopaminergic stabilizers, designed to rebuild dopamine levels in the brain to normal. Discoveries from a phase II investigation indicated that pridopidine enhanced voluntary motor function without making chorea worse.
A group of researchers led by Justo Garcia de Yebenes from the Hospital Ramón y Cajal in Madrid, Spain, carried out a phase III trial in order to further evaluate pridopidine's potential safety and effectiveness as a treatment of HD motor symptoms. 437 individuals with Huntington's disease from 8 countries in the EU participated in the trial. Patients were randomly assigned to three groups; one group received 45mg of pridopidine once daily, one group received 45mg twice daily, and the remaining group received placebo for 26 weeks.
In the initial examination, the team used a modified motor score (mMS) designed to measure 10 items associated to voluntarily movements from the unified HD rate scale (UHDRS) total motor score (TMS) to evaluate the effects of pridopidine. They also assessed UHDRS-TMS, behavior, depression and anxiety as well as cognitive function.
The team discovered that the difference in average mMS scores between the groups was not considerable after six months of treatment. However, they found that in a tertiary examination, the drug treatment resulted in improvement in total motor function, particularly in hand movements, eye movements, dystonia, gait and balance as measured by UHDRS-TMS in individuals who received the higher dose of the drug in comparison to patients given placebo.
Furthermore, additional examinations that only involved participants who completed all investigation visits and had drug compliance, more than 70% demonstrated a considerable benefit for the higher dose of the drug. Pridopidine was well tolerated and has similar adverse effects to placebo.
The researchers explain:
"Pridopidine has the potential to complement available treatments by improving a different range of motor deficits. Its lack of severe side-effects...suggests that pridopidine might be useful even for those patients who are treated at sites that are not centers of excellence for Huntington's disease."
In an associated comment, Andrew Feigin from The Feinstein Institute for Medical Research, New York, USA, said:
"A well tolerated drug that produces even small benefits for patients with Huntington's disease would be a very welcome addition to the currently available treatments for this debilitating disorder... Analysis of individual items within the UHDRS-TMS in the MermaiHD study also suggests that pridopidine might benefit features of HD for which there are currently no treatments (eye movements, hand coordination, dystonia, and gait or balance problems)."
Written by Grace Rattue