Description:
Summary
Myocardial fibrosis is a crucial marker of adverse cardiac remodeling. Research suggests a strong correlation between the extent of myocardial fibrosis and adverse myocardial remodeling that occurs after ischemic injury or during the progression of cardiomyopathies and heart failure. Diffuse myocardial fibrosis is thought to provide a high-risk substrate for the development of atrial and ventricular arrhythmias. Therefore, early detection of myocardial fibrosis might be prognostic for the development of heart failure and increased risk of both atrial and ventricular heart rhythm disorders. In addition, a means to easily assess the development of myocardial fibrosis is expected to provide a more effective way to monitor therapeutic efficacy of interventions intended to slow or halt the progression of these cardiac disorders. Although present methods can detect “frank” fibrosis, new methods that target the early stages of fibrogenesis are expected to be extremely useful as they may be more effective in guiding interventions that block further development of fibrosis and prevent the onset of myocardial remodeling associated with heart failure and arrhythmias.
Project Goals
The goal of this initiative is to significantly advance non-invasive methods to detect, image, and monitor myocardial fibrosis in vivo. Myocardial fibrosis is a hallmark of adverse cardiac remodeling associated with development of heart failure and life-threatening cardiac arrhythmias. Early detection of myocardial fibrosis is essential to development of effective ways to diagnose, treat, and prevent these cardiac disorders. Current methods for detection of myocardial fibrosis, however, are either invasive (e.g., biopsy-based) or unable to detect early fibrogenesis or diffusively distributed fibrosis in the myocardium. This initiative encourages researchers to develop innovative myocardial fibrosis detection methods that overcome current challenges and demonstrate their utility in appropriate experimental models.
Phase I Activities and Expected Deliverables
Phase I activities are expected to be aimed at demonstration of the method’s feasibility. The studies may be conducted in established animal models or human tissue samples. Examples of Phase I research and expected deliverables may include, but are not limited to:
• Design, synthesis and development of fibrosis-targeted imaging agent(s) and demonstration of the ability to detect cardiac fibrosis in well-established animal models
• Design and development of MRI-based technology/method to detect diffuse myocardial fibrosis in established experimental models
• Identification of serum biomarker(s) of myocardial fibrosis (e.g., extracellular matrix protein fragments, matrix metalloproteinases, microRNAs, post translational modified protein or glycoprotein fragments, etc.) and their limited validation using established animal models or human tissue samples Phase II Activities and Expected Deliverables
Phase II research activities are expected to include development, optimization and validation of the product/method, including research work leading to regulatory filing (IND or IDE) and help attract funding from non-federal sources. Examples of expected deliverables may include, but are not limited to:
• Development of fibrosis-targeted imaging agent(s) and data demonstrating capability to detect and quantify cardiac fibrosis in established animal models using appropriate clinical imaging platforms
• Development of MRI-based methods that enable detection and quantification of diffuse myocardial fibrosis and data demonstrating the method’s utility in established experimental models
• Validation of serum biomarker(s) for assessment and monitoring of myocardial fibrosis progression in appropriate human studies
