Laryngeal dystonia (LD), a rare neurological condition that severely disables a person’s ability to speak through involuntary spasms of the vocal cords, can be truly sickening in its impact on people’s social lives, careers, and mental well-being. At present, botulinum neurotoxin (Botox) injections for LDs are most effective in about 60% of patients, but many who receive it aren’t helped at all.
A study from researchers of Massachusetts Eye and Ear-Harvard medical school, and Massachusetts General Brigham health care system, showed that an oral medication, sodium oxybate, is better than a placebo in alleviating LD symptoms in patients whose symptoms flared after alcohol consumption. These findings were observed in the phase 2b randomized double-blind placebo-controlled 2-period crossover single-center clinical trial, published in Annals of Neurology, November 20, 2024.
“Patients with LD tell us endless stories of broken lives and careers and they desperately need new treatments. More than 80% of the patients we studied had failed other forms of treatment, and we hope our trial can give hope of a new, effective treatment for some patients to give them a good quality of life.” This neurological condition remains a mystery with patients waiting about five and half years on average before being diagnosed. Once diagnosed, treatment options are limited, often using Botox injections every 3 to 4 months for life, if they prove effective.
Simonyan’s team has previously demonstrated using previous open-label trials that sodium oxybate significantly decreases voice symptoms in 82% of alcohol-responsive LD patients. The study enrolled 106 participants with LD, 50 of whom had alcohol-responsive symptoms. A standardized alcohol challenge test was used to determine alcohol responsiveness using a controlled amount of vodka. The patients were given a single dose of 1.5g of sodium oxybate (53 patients) or a placebo (53 patients) drug for two days, matched for smell, taste, and color.
Patients with alcohol-responsive LD demonstrated significantly greater benefit from sodium oxybate compared with placebo, but not for those whose symptoms cannot be improved by alcohol. There was no difference in the efficacy of sodium oxybate in treating alcohol-responsive LD between patients with differing symptom severity (mild to severe) or with any voice symptoms, including voice tremors.
About 40 minutes after drug intake, the symptoms of voice in alcohol-responsive LD patients improved significantly and lasted up to 5 hours. No serious adverse effects and no rebound in symptoms were observed. Findings suggest that due to the better responsiveness of dystonic symptoms to alcohol, sodium oxybate could potentially be used as an effective oral treatment for other types of alcohol-responsive dystonia.
Simonyan’s team now plans to conduct a phase 3 multi-site randomized clinical trial to further assess the drug’s efficacy and safety in LD patients. Studies from her lab are also exploring whether artificial intelligence can be used to determine which patients would benefit from the treatment or alternative treatment options for patients with LD whose symptoms are not affected by alcohol consumption.
Reference: Simonyan K, O’Flynn LC, Hamzehei Sichani A, et al. Efficacy and Safety of Sodium Oxybate in Isolated Focal Laryngeal Dystonia: A Phase IIb Double-Blind Placebo-Controlled Cross-Over Randomized Clinical Trial. Ann Neurol. 2024;00:1-15. doi:10.1002/ana.27121
