An Aging Heart Model for Drug Discovery

Period of Performance: 08/15/2016 - 04/30/2017

$154K

Phase 1 SBIR

Recipient Firm

Invivo Sciences, LLC
Madison, WI 53719
Principal Investigator

Abstract

Project Summary/AbstractCardiovascular drugs are primarily prescribed to older people (>65 years of age) since theprevalence of chronic heart failure and fibrillation increases with age. The incidence of otherdiseases, including cancer and neurological disorders, increases with age, too. Any medicationshold potential risks to cause adverse events. Therefore, the risks of medications in older peoplealso increase with age. While cardiac safety of drugs is one of the primary concerns amongdrug developers and regulatory agencies, potential new drugs are tested using animal modelsof normal age. Limited progress has been made in developing a tool to predict potential cardiacsafety issues in aging heart, representing a significant unmet need in drug discovery industry.The United States will have 73 million aging population, (>65 years of age) in 2030. Thedevelopment of a computational model that can predict potential cardiac safety reactions is aplausible step towards preparing the drug discovery industry for a rapidly approaching era oflongevity. This Phase I proposal will validate and improve a computational model thatincorporate potential age-related changes in regulators of excitation contraction coupling (ECC)of cardiomyocytes (CMs) and contribution of fibroblasts (FBs) that are known to increase theirpopulation in aging hearts. The specific Aims are 1) to develop and refine a computationalmodel representing coupled FBs and CMs to simulate electrophysiology and calcium handlingof aging human heart tissue, 2) to establish human engineered heart tissues by incorporatingaging cardiac FBs and applying environmental stress that known to induce cardiac aging.These Aims are proposed to optimize a computational model, Wisdom Heart (WH) that mimicsage-associated changes in cardiac ECC of myocardium with increasing number of FBs. Thequality of WH model will be evaluated and improved against experimental data obtained frommyocardium models. The established model will be shared with the consortium organized byHESI (hesiglobal.org) with FDA, industry, and academia that is trying to improve cardiac safetyissues. The model will be incorporated to our services for conducting contract research projectsof cardiac safety assessments and drug discovery for heart failure. We have active contractswith FDA research scientists at the National Center for Toxicological Research.