An engineered macrophage-derived cytokine as a therapy for cardiac infarct

Project Lead

Professor Peter Currie, Monash University

Project Team

Associate Professor Mikael Martino, Monash University

Project Summary

Problem

Myocardial infarction (MI), commonly known as a heart attack, often leads to permanent heart muscle damage and subsequent heart failure (HF). This condition is a significant global health issue, causing high mortality and substantial healthcare costs. Current treatments primarily focus on revascularisation and symptom management, but they do not effectively address muscle cell death. There is a critical need for therapies that can regenerate heart muscle tissue post-MI to improve patient outcomes and reduce the incidence of HF.

Solution

This project aims to develop a novel protein/peptide-based therapy using Nicotinamide Phosphoribosyltransferase (NAMPT), identified in preclinical studies as crucial for muscle regeneration. NAMPT has shown promise in promoting muscle repair in zebrafish and mouse models without fibrosis or adverse immune reactions. The primary objective is to create a therapeutically relevant form of NAMPT for cardiac repair. This involves producing and purifying various NAMPT derivatives and testing their effectiveness in vitro and in mouse models of MI. The approach includes direct microinjections of NAMPT into the cardiac wall to stimulate angiogenesis, prevent cardiomyocyte death, and avoid tissue fibrosis.

Impact

A successful NAMPT-based therapy could revolutionise the treatment landscape for heart attack patients, fulfilling a critical unmet need in cardiac care. By promoting fibrotic-free heart muscle repair, this therapy has the potential to significantly improve patient outcomes, reduce mortality, and lower healthcare costs associated with heart failure. The project envisions the establishment of a spin-out company to commercialise the technology, leveraging Monash University's patents on the NAMPT cytokine and related delivery systems. Furthermore, the project will engage with stakeholders, including government, industry, and patient advocacy groups, to ensure broad dissemination and community support. This initiative represents a significant step towards developing a regenerative therapy for cardiac infarction, with substantial clinical and economic benefits