Restricted Research - Award List, Note/Discussion Page
Fiscal Year: 2023
1534 The University of Texas at Arlington (143422)
Principal Investigator: Jun Liao,jun.liao@uta.edu,(817) 272-6779
Total Amount of Contract, Award, or Gift (Annual before 2011): $ 433,120
Exceeds $250,000 (Is it flagged?): Yes
Start and End Dates: 9/1/22 - 8/31/25
Restricted Research: YES
Academic Discipline: Department of Bioengineering
Department, Center, School, or Institute: none
Title of Contract, Award, or Gift: A Controlled Septal Ablation for Inoperable Hypertrophic Cardiomyopathy
Name of Granting or Contracting Agency/Entity:
National Institutes of Health (NIH)
CFDA Link: HHS
93.837
Program Title:
NIH R15
CFDA Linked: Heart and Vascular Diseases Research
Note:
(SAM Category 1.1.1.) Hypertrophic Cardiomyopathy (HCM) is a genetic disease that results in abnormal thickening of ventricular heart muscle); particularly a bulged septum can cause left ventricular outflow tract (LVOT) obstruction. When medication alone is not sufficient to relieve symptoms, the current gold standard, septal myectomy, is performed to surgically remove excess septum with an open heart surgery. Unfortunately, many patients are poor surgical candidates and require less invasive treatment options. In these cases, cardiologists treat the patients with a minimally invasive catheterization technique called alcohol septal ablation (ASA), in which 1-4 mL of pure alcohol is injected into the septum via a septal perforator (artery) to destroy part of the septal muscle by triggering necrosis. Although ASA is a relatively common procedure for inoperable patients, it has many downfalls. Risky complications, with a periprocedural mortality rate of ~2%, include atrioventricular block, ventricular septal defect, ventricular fibrillation/tachycardia and need for pacemaker due to uncontrolled alcohol delivery resulting in varying degrees of myocardial infarction. These disadvantages of ASA represent an unmet clinical need. To overcome ASA limitations, our goal is to design a novel ablation system to replace the pure alcohol in ASA and achieve a controllable, localized septal tissue shrinkage and hence a safer ablation. The hypothesis is that the delivery of a collagenase-coated, doxorubicin-loaded, degradable nanoparticles (NPs) will allow for localized doxorubicin-induced destruction of the hypertrophic cardiomyocytes, and this single dosage delivery is able to shrink the overgrown HCM septal tissue. Three Aims will be pursued to better understand HCM septal tissue and develop this novel treatment approach: (1) Perform structural and biomechanical studies to understand the tissue and microstructural abnormalities in HCM septal tissues; (2) Develop and optimize a collagenase-coated, doxorubicin-loaded, biodegradable nanoparticle system as a new ablation means for HCM; (3) Assess the safety and efficacy of the newly developed ablation system in an HCM mouse model. The proposed research paves a new avenue to improve the safety and efficacy of septal ablation in inoperable HCM patients. The impacts are (i) the innovative concept of delivering a controllable, localized ablation to replace the unpredictable pure alcohol ablation, and (ii) the promising translational potential. This AREA project will also provide excellent NIH-funded research opportunities to our underrepresented graduate and undergraduate students at UT Arlington, a Hispanic service institute in Northern Texas.
Discussion: No discussion notes