First-in-Human Study of MANP: A Novel ANP (Atrial Natriuretic Peptide) Analog in Human Hypertension

M-atrial natriuretic peptide (MANP) is a novel ANP (atrial natriuretic peptide) analog engineered to be an innovative particulate GC-A (guanylyl cyclase A) receptor activator. The rationale for its design was to develop a best-in-class GC-A activator with enhanced cGMP activating, natriuretic, aldos...

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Bibliographic Details
Published inHypertension (Dallas, Tex. 1979) Vol. 78; no. 6; pp. 1859 - 1867
Main Authors Chen, Horng H., Wan, Siu-Hin, Iyer, Seethalakshmi R., Cannone, Valentina, Sangaralingham, S. Jeson, Nuetel, Joel, Burnett, John C.
Format Journal Article
LanguageEnglish
Published United States Lippincott Williams & Wilkins 01.12.2021
Subjects
Adult
Aged
Aldosterone - urine
Atrial Natriuretic Factor - administration & dosage
Blood Pressure - drug effects
Female
Humans
Hypertension - drug therapy
Hypertension - urine
Male
Middle Aged
Natriuresis - drug effects
Sodium - urine
blood pressure
cardiovascular disease
guanylyl cyclase
natriuresis
aldosterone
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Summary:M-atrial natriuretic peptide (MANP) is a novel ANP (atrial natriuretic peptide) analog engineered to be an innovative particulate GC-A (guanylyl cyclase A) receptor activator. The rationale for its design was to develop a best-in-class GC-A activator with enhanced cGMP activating, natriuretic, aldosterone-suppressing, and blood pressure–lowering actions, compared with endogenous ANP, for the treatment of hypertension. Here, we report the first-in-human study on the safety, tolerability, neurohumoral, renal, and blood pressure–lowering properties of MANP in hypertension subjects. This was an open-label sequential single ascending dose design in which all subjects stopped all antihypertensive agents for 14 days before receiving a single subcutaneous injection of MANP. MANP was safe, well tolerated, activated cGMP, induced natriuresis, reduced aldosterone, and decreased blood pressure at or below the maximal tolerated dose. Thus, MANP has a favorable safety profile and produced expected pharmacological effects in human hypertension. Our results support further investigations of MANP as a potential future blood pressure–lowering, natriuretic and aldosterone-suppressing drug for hypertension especially resistant hypertension.
ISSN:0194-911X
1524-4563
DOI:10.1161/HYPERTENSIONAHA.121.17159