Deep brain stimulation (DBS) with implantable electrodes has been used for reduction of ethanol abuse and drug-seeking behaviors in Europe [14]. The use of such deep-brain stimulation procedures has been problematic because of concerns about invasiveness of the procedure. Applicant has developed a new noninvasive method of transporting magnetic particles directly to target sites within the brain. We propose to use this method to place magnetic particles in brain locations where DBS studies have shown reductions in drug-seeking behavior. Once placed, the magnetic particles can be activated through external application of magnetic fields to stimulate neurons mechanically. When translated into clinical use, magnetic activation could be performed with a wearable device, as has been done for other neurological conditions (migraine, epilepsy). The particles are designed to degrade over a pre-selected time interval (e.g., six-months). In this proposal, we will demonstrate the short-term safety and efficacy of the construct in an rodent model of opiate relapse after a period of abstinence. Efficacy will be measured by quantifying reinstatement of drug-seeking behavior. The results of this collaborative work will lay the foundation for Phase II studies, which will provide information needed for human trials.
Public Health Relevance Statement: Summary Deep brain stimulation with implantable electrodes has been used for reduction of ethanol abuse and drug-seeking behaviors in Europe. The use of such deep-brain stimulation procedures has been problematic because of concerns about invasiveness of the procedure. Company proposes to develop a noninvasive replacement for electrode- based deep brain stimulation.
Project Terms: Abstinence; Acute; addiction; Afferent Neurons; Alcohol abuse; Animal Model; animal mortality; Animals; Attenuated; base; Bilateral; Brain; Capital; Catheters; Clinical; Cocaine; commercialization; Deep Brain Stimulation; density; design; Devices; dosage; Dose; dosimetry; drug seeking behavior; Dyes; Electrodes; Epilepsy; Equipment; Europe; Evaluation; FOS gene; Foundations; Funding; Future; Goals; Histology; Human; image guided; Immediate-Early Genes; Implant; implantation; improved; Injectable; Intervention; Intranasal Administration; Iron; Location; magnetic field; Magnetism; Measures; Mechanical Stimulation; Mechanics; Methods; Migraine; Neurologic; Neurologist; Neurons; Neurosurgeon; Nucleus Accumbens; Opioid; particle; Patients; Penetration; Pharmaceutical Preparations; Phase; phase 2 study; Prefrontal Cortex; Preparation; Price; Procedures; Protocols documentation; Prussian blue; Publishing; radiologist; Rattus; Recommendation; Relapse; Residual state; Resolution; response; Rodent Model; Safety; Self Administration; Site; Small Business Technology Transfer Research; Specialist; Supervision; Symptoms; Synapses; System; time interval; Toxic effect; Training; Translating; treatment center; wearable device; Work
