IND-Enabling Studies for Targeted Phase Shift Microbubbles for Sonothrombolysis
Abstract
One person dies every 36 seconds in the United States from cardiovascular disease. About 659,000 people in the United States die from heart disease each year, that is 1 in every 4 deaths. Although these numbers have decreased somewhat, people are still dying from heart attacks or acute myocardial infarction (AMI). Treatment for MI ranges from lifestyle changes and cardiac rehabilitation to medications, stents, and bypass surgery. Often stents, angioplasty or a minimally invasive procedure such as percutaneous coronary intervention, (PCI) are performed. The risks of PCI are the complications that may be consequent to the procedure and induce the detachment and generation of small blood clots lodging themselves in the arteries and creating an obstruction called microvascular obstruction of microvascular obstruction (MVO). MVO leads to worse clinical outcomes. There is no consistent therapy, and MVO occurs in up to 60% of patients post-PCI, despite successfully restoring blood flow in the major arteries. We have developed ultrasound targeted microbubbles that are condensed in smaller size bubbles (also herein referred as phase shift microbubbles PSMB, in the size of the nanometer, 1/10th the size of microbubbles) that are able, when given in an intravenous injection, to travel directly to the clot, and upon entry in the ultrasound field applied externally, disrupt the clot and restore the blood flow and eliminate the clot. In addition, we have engineered these agents to carry a material that causes these small bubbles to bind tightly and directly to the clot so that very low doses are needed and allow clots to be dissolved very quickly when ultrasound is applied. We have obtained proof-of-concept results in animals (rats and pigs) for this technology. This innovative treatment is being explored as a potentially exciting and promising treatment option for patients who have AMI with MVO. This project will support the development of a novel less-invasive treatment technology for associated cardiovascular conditions in the primary Topic Area of Cardiovascular Health. Veterans are at greater risk of heart disease than the general population. There is great potential of this technology to improve outcomes in Veterans with coronary artery disease to effectively treat MVO. Also relevant to the military in duty, the technology may be used remotely where other treatments are not available. The major goals of the proposal are the following: (1) test the new product in animals and determine the best conditions (concentration and parameter of ultrasound); (2) to produce in high amounts the product so that it would be ready to be tested in agreement with the regulations for the clinic in humans, (3) test the product to make sure it is safe and doesn’t exhibit side effects, (4) request an early meeting with the U.S. Food and Drug Administration (FDA) to obtain their guidance as to what other studies are needed to have this product accepted to be tested in humans and start the clinical trial, and (5) perform these recommended toxicology studies and file the entire package at the FDA to request the authorization to test the product in humans with their required supplementary animal data. Our team has the expertise in the field of ultrasound contrast agent as well as in cardiovascular research and clinical trials. The project is poised to be successful considering the preliminary results acquired to date, the team of experts assembled for this proposal, the proposed experiments, and the realistic timeline. The ultimate goal is to move the product through the required regulatory procedures and obtain the authorization from the FDA for a clinical trial for patients afflicted with AMI.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310893
Entities
People
- Emmanuelle Meuillet
Organizations
- United States Army