ATTUNE NEUROSCIENCES INC — Department of Health and Human Services SBIR Phase I: NIDA

Description

Summary The opioid use disorder (OUD) is a rapidly expanding health epidemic in the United States with little progress in treatment efficacy. Insufficient sleep represents the most severe and pervasive symptoms of both phases of withdrawal and persist despite treatment. Because sleep loss plays a key role in anxiety and daily routine, its disruption is a major factor in a patient’s relapse evidenced by the higher incidence of relapse in OUD patients with sleep disorders. Sleep dysfunction in OUD is characterized by significant loss in slow wave sleep (SWS), which are critical components of the benefits of sleep. In patients with severe withdrawal, sleep may consist almost entirely of brief periods of rapid eye movement (REM) with sparse non-REM (NREM) sleep interrupted by numerous awakenings. Given the prevalence of poor sleep quality in OUD and the association with relapse, treatments enhancing the restful effects of sleep could reduce the rate of relapse. However, commonly prescribed sleep medications have sedative and hypnotic effects with a risk of dependency too great for patients with OUD. Thus, new interventions to augment sleep are a critical unmet medical need which could have an outsized influence on their life. Here, we build off of research in humans and animal models demonstrating that focused ultrasound can stimulate brain regions underlying SWS. We will design a wearable device integrating sleep recordings and steerable ultrasound arrays. Ultrasound arrays will target the thalamus, a core SWS structure, using MRI maps of patient’s brains and skulls. We will design custom EEG analytics software for delivering the stimulus during the rising phase of slow waves to enhance wave amplitude, duration, and beneficial effects. We will perform a human factors study with OUD patients to assess comfort and usability for redesigning the wearable. Throughout the project we will interact with the FDA in efforts to gain approval for a phase II study with OUD patients.Project narrative Sleep issues are a primary cause of relapse in opioid use disorder patients. While there are numerous pharmacological strategies for enhancing sleep, the addictive nature of these compounds poses a significant threat to patients with addiction proclivity. We will develop an ergonomic wearable device for enhancing sleep through targeted focused ultrasound stimulation of the brain. The device will use an integrated EEG to identify and enhance slow wave sleep patterns through stimulation of the thalamus using patient specific brain maps. We will work with both OUD subjects and the FDA to identify the necessary steps for making the device both safe and usable for a phase II study and future commercialization.