This Phase I SBIR develops and tests an Oscillated Syringe for Intracranial Injections (OSII) of viral constructsfor chemogenetic studies of alcohol addiction neurocircuitry in the brain. The project's long-term goal is todevelop and commercialize a surgical tool to enable reliable and safe injections of viral constructs into thebrain for preclinical studies, and eventually clinical therapeutic approaches. Actuated Medical, Inc. (AMI)develops innovative motion devices incorporating electronically-controlled actuator technologies to improvepatient outcomes and advance medical research. This work is in collaboration with Drs. K. Grant and V. CuzonCarlson 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 in2020 - 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 canilluminate 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 viralconstructs can be targeted to specific brain regions, to maximize and precisely control designer receptorexpression. In a recent preclinical study targeting DREADD receptors to the nucleus accumbens, the percentof targeted cells expressing the DREADD receptor ranged from 41-87%. This poor delivery accuracysignificantly 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 neuralimplant insertion technology which enables low-force, low-friction insertion of probes and electrodes into thebrain. The goals for the OSII system are 1) reduce insertion force, 2) enable use of smaller and more flexibleviral injection syringes, including the potential for blunted tips, 3) reduce tissue damage, 4) reduce risk of virusmigration 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 targetsusing vibration with and without intact dura. Acceptance Criteria: >70% reduction in insertion force comparedto non-vibrated insertion, and <1 mm deviation from target path with 5 cm deep insertions using 25-36Gpolyimide and metal cannulas in models. 100% insertion success through dura with 36G metal cannula. Aim 2Demonstrate OSII improves viral vector delivery to targets with less off-target spreading and DREADD receptorexpression in preclinical model. Acceptance Criteria: Improved mean percentage (>55%) of DREADD receptorexpression restricted to the target tissue with viral injection via OSII (as compared to previous study).
Public Health Relevance Statement: Project narrative:
Alcohol addiction is a major public health burden. DREADDs (designer receptors exclusively activated by
designer drugs) are chemogenetic tools primarily used for neuroscience research, but recently appreciated for
their potential as therapeutic for neurological disorders, including addictive behaviors like alcohol addiction. A
complication of the implementation of chemogenetic tools is that viral vectors must be reliably delivered to
target brain structures for precise viral expression. This project will develop and commercialize a system that
leverages oscillation of a thin injection cannula for reduced insertion and friction forces, improving the targeting
and reliability of injections to precise brain locations.
Project Terms:
|
