Oscillated Insertion Tool for Minimally Invasive, Low-Damage, Accurate Placement of Delivery Cannula to Improve Efficacy for DREADDS Therapy in Alcohol Addiction Treatment

点击翻译按钮获取中文摘要

This Phase I SBIR develops and tests an Oscillated Syringe for Intracranial Injections (OSII) of viral constructs for chemogenetic studies of alcohol addiction neurocircuitry in the brain. The project’s long-term goal is to develop and commercialize a surgical tool to enable reliable and safe injections of viral constructs into the brain for preclinical studies, and eventually clinical therapeutic approaches. Actuated Medical, Inc. (AMI) develops innovative motion devices incorporating electronically-controlled actuator technologies to improve patient outcomes and advance medical research. This work is in collaboration with Drs. K. Grant and V. Cuzon Carlson at the Oregon Health and Science University (OHSU). Public Health Problem: Alcohol addiction is estimated to affect 28 million Americans over the age of 12 in 2020 – and is subject to relapse rates of 40-60% despite available pharmaceutical and psychosocial therapies. Chemogenetic tools have significant potential to lead to translational findings in preclinical research that can illuminate mechanisms underlying alcohol pharmacology and addiction. However, the utility of chemogenetics, such as designer receptors exclusively activated by designer drugs (DREADDs), is limited by how well the viral constructs can be targeted to specific brain regions, to maximize and precisely control designer receptor expression. In a recent preclinical study targeting DREADD receptors to the nucleus accumbens, the percent of targeted cells expressing the DREADD receptor ranged from 41-87%. This poor delivery accuracy significantly impacted subsequent behavioral outcomes and prevented conclusive study hypothesis testing. Solution: This project commercializes the OSII to improve targeting and viral expression in preclinical studies, initially examining the neural circuitry underlying alcohol addiction. AMI will leverage its oscillated neural implant insertion technology which enables low-force, low-friction insertion of probes and electrodes into the brain. The goals for the OSII system are 1) reduce insertion force, 2) enable use of smaller and more flexible viral injection syringes, including the potential for blunted tips, 3) reduce tissue damage, 4) reduce risk of virus migration to other tissues along the syringe insertion track, and 5) allow insertion through the dura. Aim 1 Demonstrate accurate placement of 25-36G micro-injection cannulas in simulated deep brain targets using vibration with and without intact dura. Acceptance Criteria: >70% reduction in insertion force compared to non-vibrated insertion, and <1 mm deviation from target path with 5 cm deep insertions using 25-36G polyimide and metal cannulas in models. 100% insertion success through dura with 36G metal cannula. Aim 2 Demonstrate OSII improves viral vector delivery to targets with less off-target spreading and DREADD receptor expression in preclinical model. Acceptance Criteria: Improved mean percentage (>55%) of DREADD receptor expression restricted to the target tissue with viral injection via OSII (as compared to previous study).