helping patients with heart failure
Heart failure, specifically myocardial contractile dysfunction, is the leading cause of death worldwide. Those affected by heart failure experience a deteriorating lifestyle, shortened life span, and ultimately death. The American Heart Association estimates more than 8 million adults in the U.S. will be affected by heart failure by 2030, imposing a devastating economic cost and tremendous human suffering. Aside from heart transplants, there is no cure for heart failure. In order to advance treatment options for patients with heart failure, more must be understood about the mechanisms underlying cardiac performance.
University of Michigan’s Ruthann Nichols, Ph.D., has discovered RFRP-1Rantgpr as an effective and safe novel therapeutic that will improve cardiac function in heart failure patients. When targeted, this pathway in the human heart improves contractile performance safely and without inducing arrhythmias, unlike many of the drugs currently on the market, making RFRP-1Rantgpr a novel and effective progenitor molecule for drug development.
Nichols explains she “designed RFRP-1Rantgpr as an antagonist to RFRP-1R, to improve cardiac function. It increases contractile performance in heart failure models and in human cardiomyocytes safely without inducing arrhythmia.”
The current standard of care for heart failure includes a 2-3 drug strategy of vasodilators, diuretics, and, possibly, inotropes. At best, these treatments lessen the symptoms but are not cures and often lead to re-hospitalization. The current solutions fail because none effectively addresses the mechanisms underlying cardiac performance.
RFRP-1Rantgpr, an antagonist to RFRP-1R signaling, targets a novel cardiac G protein-coupled receptor (GPCR) pathway underlying contractile performance. The 5-amino acid antagonist, which improves cardiac function safely and without inducing arrhythmia, is easily synthetized and proteolytically resistant.
Approximately 34 percent of the drugs currently on the market target a GPCR, yet, while there is a critical need for an effective and safe heart failure therapeutic, no drug targets the RFRP-1R GPCR signaling pathway. Nichols’ antagonist, RFRP-1Rantgpr, is the first drug progenitor molecule that targets this novel human GPCR pathway to improve contractile performance safely without inducing arrhythmia.
- Intellectual Property: Patent approved
- Commercialization Strategy: Identify venture capitalists and industry interest; submit an SBIR/STTR with the intent to license to an existing company or start-up company
- Regulatory Pathway: Additional testing to obtain FDA approval; filing an Investigational New Drug (IND) application
- Engage Investors: FDA and IND approval will attract investors for a start-up or industry interest to license the technology
- Product Launch Strategy: Test effectiveness, safety, and toxicity in human cardiomyocytes following FDA recommendations and in a human disease model to facilitate developing RFRP-1Rantgpr as a heart failure drug
- Investigate the effects of RFRP-1Rantgpr in a model for progressive onset of human hypertension and heart failure
- Measure the effect of RFRP-1Rantgpr on disease-state cardiomyocytes
- Establish the in vivo safety of RFRP-1Rantgpr
- Collect concentration-time data for RFRP-1Rantgpr clearance
- (Completed as part of MTRAC funding) Examine RFRP-1Rantgpr effectiveness, safety, and cardiotoxicity in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
- Evaluate the effects of RFP-1Rantgpr
- Evaluate the cellular effects of RFP-1Rantgpr in ischemic-like hiPSC-CMs