Targeting stromal progenitors to prevent the development of heart failure
Grant Award Details
Grant Type:
Grant Number:
TRAN1-12893
Investigator(s):
Disease Focus:
Award Value:
$4,714,824
Status:
Closed
Progress Reports
Reporting Period:
Final Operational Milestone #5 2023
Reporting Period:
Final Operational Milestone #6 PPAC 2024
Grant Application Details
Application Title:
Targeting stromal progenitors to prevent the development of heart failure
Public Abstract:
Translational Candidate
Monoclonal antibody targeting Ectonucleotide phosphodiesterase/pyrophosphatase 1 (ENPP1)
Area of Impact
Heart disease: To prevent the development of heart failure after heart attacks
Mechanism of Action
After myocardial infarction, myofibroblast progenitors express ENPP1. ENPP1 is a type II transmembrane protein that hydrolyzes extracellular ATP and hydrolytic products generated by ENPP1 initiate an inflammatory cascade that worsens cardiac repair. The monoclonal antibody would bind to and inhibit ENPP1 on myofibroblast progenitors to decrease inflammation and scarring and augment heart repair and post injury heart function after myocardial infarction.
Unmet Medical Need
Approximately 6 million people in the United States have heart failure (HF) and once a diagnosis of HF is made, approximately 50% survive 5 years. There is thus an unmet need for developing novel therapeutics for HF. The agent being developed will prevent the development of HF after heart attacks.
Project Objective
Pre IND meeting
Major Proposed Activities
Monoclonal antibody targeting Ectonucleotide phosphodiesterase/pyrophosphatase 1 (ENPP1)
Area of Impact
Heart disease: To prevent the development of heart failure after heart attacks
Mechanism of Action
After myocardial infarction, myofibroblast progenitors express ENPP1. ENPP1 is a type II transmembrane protein that hydrolyzes extracellular ATP and hydrolytic products generated by ENPP1 initiate an inflammatory cascade that worsens cardiac repair. The monoclonal antibody would bind to and inhibit ENPP1 on myofibroblast progenitors to decrease inflammation and scarring and augment heart repair and post injury heart function after myocardial infarction.
Unmet Medical Need
Approximately 6 million people in the United States have heart failure (HF) and once a diagnosis of HF is made, approximately 50% survive 5 years. There is thus an unmet need for developing novel therapeutics for HF. The agent being developed will prevent the development of HF after heart attacks.
Project Objective
Pre IND meeting
Major Proposed Activities
- Development of a stable cell bank for antibody production
- Upstream and downstream process development
- Dose range finding studies
Statement of Benefit to California:
Cardiovascular disease remains a leading cause of death in California and accounts for nearly one third of all deaths. The prevalence of heart disease is close to 25% in individuals above the age of 75 and 7% of individuals above the age of 65 suffer from heart failure. Heart attacks are the leading cause of heart failure and the therapeutic agent developed here will prevent the development of heart failure after heart attacks and of immense benefit to Californians.
