Natriuretic peptide analogues with vasodilatory or renal activities for personalized care of heart failure patients
Heart failure (HF) is a common, costly, frequently fatal condition and the leading cause of hospitalization in people older than 65, HF afflicts 38 million people worldwide and is responsible for ~25% deaths. Because of its earlier onset, new management strategies are needed in Asia. The course of chronic HF is punctuated by recurrent episodes of life threatening acute decompensated HF (ADHF) an abrupt deterioration characterized by hemodynamic instability, and pulmonary oedema, often associated with decline in renal function. Not all HF patients have similar volume–pressure derangement. Two-thirds of ADHF are “warm and wet”, in which arterial pressure and peripheral tissue perfusion are relatively preserved but pulmonary and peripheral edema are present. The critical “cold and wet” state, with volume expansion, pulmonary and/or peripheral edema and relative hypotension and impaired peripheral perfusion, increases the rate of death by 2.5 fold.
Unfortunately, no new therapeutic agents for ADHF have been introduced for 30 years and existing therapies cannot be individualized to treat each phenotype precisely. A major unmet need therefore exists for therapeutic agents allowing controlled vasodilation without excess diuresis, which risks rebound into volume depletion and kidney injury at one end of the spectrum and effective diuresis to remedy volume overload and edema without excess lowering of blood pressure which risks hypo perfusion of vital organs, at the other end.
With a long-term intention to provide better treatment for ADHF patients, this team will evaluate two proprietary distinct classes of natriuretic peptide analogues (NPAs) – one with exclusive vasodilatory effects without diuresis and the other with exclusive diuretic effects without vasodilation, in well-established normal and ADHF sheep models as a prelude to first-in-human trials.
Principal Investigator: Prof Mark Richards
Institution: National Cancer Centre Singapore
NHIC Ref: NHIC-I2D-1612150