Kristina Simonyan, MD, PhD, from the Icahn School of Medicine at Mount Sinai, has received more than $5 million from the National Institutes of Health (NIH) to study spasmodic dysphonia (SD), a neurological disorder characterized by vocal cord spasms. Dr. Simonyan is studying the causes and disease pathology of SD in hopes of identifying new drug targets to address a significant unmet need for treatments in people with this debilitating disorder.
To develop new treatment options for patients with SD who failed available options, Dr. Simonyan's team is examining the central mechanisms of action of a novel oral medication, sodium oxybate, which is FDA-approved for narcolepsy. Anecdotally, about 20 percent of SD patients have positive effects of alcohol on their voice symptoms. Research shows that patients whose condition improves by drinking alcohol benefit from taking sodium oxybate because it acts on the brain through the same mechanisms as alcohol.
SD develops spontaneously in midlife and progresses to become a chronic condition. It is characterized by interruptions in speech and can cause the voice to break up, sound strained or breathy, but without any damage to the vocal cords or throat. The causes and disease biology of SD are unknown, and the treatment is limited to symptomatic management of the disorder, such as with repeated injections of botulinum toxin into the affected muscles of the voice box, which does not work for all patients. The injections also have side effects that cause the person to lose their voice altogether for some time before they see improvement.
"Spasmodic dysphonia can have a terrible impact on quality of life, often causing emotional stress, social embarrassment, isolation, and even loss of employment," said Dr. Simonyan, who is an Associate Professor of Neurology and Otolaryngology at Mount Sinai. "A better understanding of the disease and how to treat it is desperately needed to help us find a cure, rather than only treating the symptoms of it."
By combining high-resolution brain imaging and next-generation whole exome sequencing, Dr. Simonyan's team is examining genetically modified differences in brain abnormalities in 240 patients with different types of SD. The team also is evaluating how people with SD perceive and process different sensory stimulations, such as flashing lights, smells and sounds, and how they integrate (or fail to integrate) this information with motor control of their speech production. By understanding the interactions between brain organization, genetic susceptibility and risk factors, sensory input and motor output, the researchers hope to identify diagnostic biomarkers of this disorder. Biomarkers are needed to prevent misdiagnoses, and for detection and evaluation of SD patients as well as screening of people at risk for SD development.
"The use of advanced neuroimaging methodologies together with extensive analyses of brain functional and structural organization in these patients is anticipated to yield novel results, which will be critical for the establishment of criteria for improved clinical management of this disorder," said Dr. Simonyan.