Clinically translating ultrasonic CSF clearing to enhance brain resilience

Recent data suggest that increased circulation of cerebrospinal fluid (CSF) to clear the brain and spinal cord of waste is associated with improved outcomes in aging and recovery from brain injury, suggesting that inducing CSF clearing could enhance brain resilience. However, a therapeutic modality for directly inducing CSF clearing has not been available. Recently, this research team has shown that a low intensity, noninvasive therapeutic ultrasound protocol increases CSF clearing in rodents. Application of this protocol in rodent aging and hemorrhagic injury models yields clearing of brain waste products, decreased neuroinflammation, decreased brain swelling, improved functional recovery, and improved survival. The team proposes to develop an ultrasound system that could apply this protocol in human subjects. Then, through a first-in-human trial in healthy older volunteers, evaluate the safety and feasibility of this approach, while evaluating for therapeutic effects on processes associated with increased CSF clearing: sleep, brain-to-blood waste clearance, and MRI markers of CSF circulation. With success in this program, the team will have clinically translated a novel, noninvasive, and non-pharmacologic approach for inducing CSF clearing, established its safety, and estimated its effect size for affecting processes integral to brain resilience, enabling larger clinical trials to determine its efficacy to treat disorders of aging.