The oral drug sodium oxybate shows promise for the treatment of laryngeal dystonia

The oral drug sodium oxybate shows promise for the treatment of laryngeal dystonia

Laryngeal dystonia (LD), a rare neurological disorder that significantly affects a person's ability to speak due to uncontrollable vocal cord spasms, can have a debilitating impact on a person's social life, employment, and mental health. Currently, LD is most commonly treated with botulinum neurotoxin (Botox) injections, but this treatment is ineffective in up to 40% of patients who receive it. Now, a study conducted by researchers at Mass Eye and Ear, a member of the Mass General Brigham Health System, shows that an oral medication, sodium oxybate, is more effective than a placebo at reducing LD symptoms in patients whose symptoms improve when they consume alcohol.

The results of the randomized phase 2b clinical trial were published on November 20 inAnnals of Neurologybuild on more than a decade of research inspired by anecdotal reports from patients with LD who reported that their symptoms improved after consuming a few alcoholic beverages. Sodium oxybate is a central nervous system agent approved by the FDA to treat patients with narcolepsy and sleep disorders. Sodium oxybate mimics some of the effects of alcohol.

In the study of more than 100 patients, a single dose of sodium oxybate significantly improved the symptoms of patients with alcohol-sensitive LD without causing serious side effects. The minimal effectiveness of the drug was 16% in voice improvement, with an average of 41% in patients with alcohol-sensitive LD. Sodium oxybate showed no significant changes compared to placebo in LD patients whose symptoms did not improve with alcohol.

We hear many stories of shattered lives and careers from patients with laryngeal dystonia who were desperate for new treatment options. Our study gives us hope that a new, effective treatment can be offered to some of these patients. There is a lot of interest from the dystonia community and we receive many calls from patients asking, “When will this drug be available?” How can I get a prescription?’”

Kristina Simonyan, MD, PhD, Dr. med,main author,Vice Chair for Clinical Research in the Department of Otolaryngology-Head and Neck Surgery at Mass Eye and Ear and Professor of Otolaryngology-Head and Neck Surgery at Harvard Medical School

Laryngeal dystonia, formerly known as spasmodic dysphonia, is a rare disorder that affects over 50,000 people in the United States and Canada. It is more common in women than men and typically occurs around the age of 40, often having a significant impact on quality of life. The exact neurological cause is unknown and it takes an average of up to 5.5 years for patients to receive a correct diagnosis. Once diagnosed, treatment options are limited to lifelong Botox injections every three to four months, provided they are effective.

In previous open-label studies, Simonyan's team showed that sodium oxybate improved voice symptoms in 82% of patients with alcohol-sensitive LD. In their new study, the team wanted to confirm the drug's effectiveness in a more rigorous comparison with a placebo using a double-blind, randomized clinical trial design.

Researchers recruited 106 participants with LD, 50 of whom had alcohol-related symptoms. Response to alcohol was determined by a standardized alcohol challenge test using a controlled amount of vodka. Participants traveled from across the US, UK and Canada to take part in the study - a testament to the excitement this medication is generating in the dystonia community. Over a period of two days, each patient received a single dose of 1.5 g of sodium oxybate or a placebo that matched the drug in taste, smell, color and appearance. The study was double-blind, meaning neither the patient nor the doctor knew when they were receiving the active drug. To test the effectiveness of the treatment, the team assessed patients' vocal symptoms before treatment and at various intervals after treatment.

Sodium oxybate reduced symptoms significantly more effectively than placebo in patients with alcohol-responsive LD, but not in patients whose symptoms did not improve with alcohol. The effectiveness of sodium oxybate in alcohol-responsive LD did not differ between patients with varying degrees of symptom severity (mild to severe) or those who had additional vocal symptoms such as vocal tremor.

Vocal symptoms in LD patients who responded to alcohol improved significantly about 40 minutes after taking the medication, with benefits lasting up to 5 hours. Although some patients experienced mild and transient side effects such as nausea, dizziness and daytime sleepiness, there were no serious adverse events after the drug wore off and no rebound in symptom severity.

"Our results suggest that sodium oxybate can be taken as needed, such as before work or a social event, allowing patients to tailor treatment to their own daily needs and get their symptoms under control," Simonyan said.

Going forward, Simonyan's team plans to conduct a phase 3, multisite, randomized clinical trial to further evaluate the drug's efficacy and safety in LD patients. Her lab is also conducting artificial intelligence studies to identify which patients might benefit from the treatment, as well as alternative treatments for LD patients whose symptoms do not respond to alcohol.

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