R44AA030512

Oscillated insertion tool for minimally invasive, low-damage, accurate placement of delivery cannula to improve efficacy for DREADDs therapy in alcohol addiction treatment - this Phase II SBIR further develops the Oscillated Syringe for Intracranial Injections (OSII) system to deliver low-force, high-accuracy placement of cannulas for drug and viral vector infusions to the central nervous system.

The project: a) moves the system toward clinical use, including an FDA pre-submission; and b) completes testing required to market the device to the neuroscience community as a research tool. Actuated Medical, Inc. (AMI) will collaborate with key staff at the Oregon Health and Science University and Penn State University for development and validation tasks, including a critical adeno-associated virus (AAV) study.

Public health problem: Treating substance abuse remains a major challenge in the U.S. and worldwide. Counselling approaches experience high relapse rates. Pharmacological interventions such as naltrexone are subject to inconsistent use and are not safe for patients with compromised renal and liver function.

AAV potential: Recent expansion of gene editing tools such as CRISPR, and delivery of stable gene expressing plasmids through new delivery methods with cell-type specificity, such as recombinant AAVs, have shown promise for treating previously intractable diseases. Research focused on addiction has produced promising behavioral changes, but variability in regional AAV expression due to current delivery methods results in too much uncertainty for clinical viability.

This is in part due to needle deflections during insertion, as well as bolus spread through perivascular spaces and backwards along large needle tracks. New surgical devices and methods are needed that can achieve the specificity of viral infusion needed for clinical use. OSII will simplify, standardize, and improve intracranial injections for pharmacology or viral-vector delivery.

Axial vibration of the cannula reduces insertion force and buckling, allowing use of smaller infusion cannula, reducing damage to regions along the needle track, and minimizing aliquot backflow during needle withdrawal. Product innovation: OSII uses electronic control to maintain device oscillation at resonance frequency for long (up to 30 cm) insertions. Precision tight coupling allows transmission of the vibration to the cannula.

Long-term goal: Phase II validates behavioral modification following gene therapy with OSII-delivered vectors in a preclinical model and conducts an FDA pre-submission discussion. Future projects obtain an Investigational Device Exemption (IDE) for first-in-man trials of OSII as a delivery tool to treat addictive behavior.

Aim 1. Advance usability of OSII through development of improved syringe coupling and user control mechanisms. Aim 2. In vivo validation of neural circuit modulation using OSII-delivered DREADDs. Aim 3. In vivo validation of behavioral modulation using OSII-delivered DREADDs in attentional set-shift task and schedule-induced polydipsia paradigms. Aim 4. Confirm safety and efficacy of OSII system through verification and validation (V&V). Conduct pre-submission discussion with the FDA.

Actuated Medical

NOT APPLICABLE

93.273 - Alcohol Research Programs

National Institute on Alcohol Abuse and Alcoholism (NIAAA) [HHS - NIH]

Bellefonte, Pennsylvania 168238445 United States

Single Zip Code

PHS 2023-2 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed) (PA-23-230)

Amendment Since initial award the total obligations have increased 204% from $1,001,961 to $3,042,183.