?Dysphagia refers either to the difficulty with the initial phases of a swallow or to the sensation that foods and or liquids are somehow being obstructed in their passage from the mouth to the stomach. As many as 600,000 Americans are newly diagnosed with dysphagia each year, primarily as a result of neurological diseases like amyotrophic lateral sclerosis (ALS), stroke, dementia, Parkinson's disease, muscular dystrophy, and cerebral palsy. Approximately 60-80% of patients with neurodegenerative disease are affected by dysphagia. Dysphagia is highly correlated with malnutrition and aspiration pneumonia, which result in poor quality of life and contributes significantly to increased morbidity and mortality. Current treatments for this debilitating and life-threatening condition ar limited to diet modifications (e.g., thickened liquids), behavioral adaptations (e.g., tucking the chin when swallowing), and other palliative interventions (e.g., feeding tubes) as efforts to extend survival. Despite being a major source of morbidity and mortality for a myriad of neurologic conditions, there are few treatment options for dysphagia. nUro, Inc. ("nUro") - in collaboration with Dr. Teresa Lever (University of Missouri) - is developing implantable neurostimulation technology to provide a new treatment option for patients with dysphagia. The nUro technology targets the superior laryngeal nerve (SLN), which contains predominantly sensory nerve fibers that relay information about temperature, taste, and touch from the larynx and pharynx to the brain. Nerve signals traveling from the SLN to the brain contribute to the orchestration of the triggering, shaping, and timing of the sequential motor pattern of swallowing. We hypothesize that chronic SLN stimulation will selectively facilitate swallowing in patients with neurogenic dysphagia. The broad, long-term objective of this proposed research is to establish SLN stimulation as a novel and effective preventative/restorative treatment for dysphagia in ALS and other chronic neurological conditions that cause dysphagia-associated morbidity and mortality. The immediate goal of the proposed application is to optimize a protocol for chronic SLN stimulation in a mouse model of ALS. In this Phase 1 proposal, we will demonstrate the feasibility of chronic SLN stimulation therapy by investigating the efficacy of this innovative approach to maintain healthy swallowing function in a transgenic mouse model of ALS. By identifying the appropriate treatment parameters in unanesthetized, ambulatory mice (Specific Aim 1) and demonstrating that ALS-affected mice can maintain healthy swallowing function and survive significantly longer as a result of chronic SLN stimulation (Specific Aim 2), we will establish the feasibility necessary to begin investigation and development of a human therapy for dysphagia in ALS. Results will lay the groundwork for using chronic SLN stimulation for long-term management of dysphagia in patients with ALS and other chronic neurological conditions that cause dysphagia-associated morbidity and mortality.
Public Health Relevance Statement: Public Health Relevance: Dysphagia, the perception that there is an impediment to the normal passage of swallowed material, causes significant morbidity and mortality in as many as 15 million Americans each year. For most of these patients, dysphagia is secondary to neurodegenerative diseases like amyotrophic lateral sclerosis (ALS), stroke, and Parkinson's disease. We propose to develop an implantable technology that will facilitate swallowing through coordination and enhancement of the nervous system, thereby restoring quality-of-life and mitigating both morbidity and mortality in patients suffering from dysphagia.
NIH Spending Category: ALS; Brain Disorders; Dental/Oral and Craniofacial Disease; Digestive Diseases; Neurodegenerative; Neurosciences; Nutrition; Rare Diseases
Project Terms: Acute; Admission activity; Adverse effects; Affect; afferent nerve; aging population; American; Amyotrophic Lateral Sclerosis; Animal Model; Animals; Aspiration Pneumonia; awake; Behavioral; Biological Process; Brain; Brain Stem; Cerebral Palsy; Chin; Chronic; Clinical; Collaborations; Complex; Cranial Nerves; Deglutition; Deglutition Disorders; Development; Diet Modification; Disease; Effectiveness; Electric Stimulation; Enteral Feeding; Epilepsy; Esthesia; Food; Frequencies (time pattern); Future; Goals; Healthcare; Hospitals; Human; Impairment; innovation; Intervention; Investigation; Knowledge; Larynx; Lesion; Life; Liquid substance; Malnutrition; Medical; Methods; Missouri; Morbidity - disease rate; Mortality Vital Statistics; Motor; mouse model; Mus; Muscular Dystrophies; Nerve Fibers; nervous system disorder; Nervous system structure; Neurodegenerative Disorders; Neurologic; Neurons; neurotransmission; Newly Diagnosed; novel; Nucleus solitarius; Oral cavity; palliative; Parkinson Disease; Parkinson's Dementia; Patients; Pattern; Perception; Pharyngeal structure; Phase; Physiology; Protocols documentation; public health relevance; Quality of life; Reflex action; Refractory; Research; research study; restorative treatment; Role; Secondary to; Sensory; sensory input; Shapes; Source; Staging; Stimulus; Stomach; stroke; Structure of superior laryngeal nerve; Taste Perception; Technology; Temperature; Time; Touch sensation; Transgenic Mice; Translations; Travel; Universities; vagus nerve stimulation; Vagus nerve structure; Wakefulness
