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

Author:

Chen Horng H.1ORCID,Wan Siu-Hin2,Iyer Seethalakshmi R.1,Cannone Valentina3,Sangaralingham S. Jeson1ORCID,Nuetel Joel4,Burnett John C.1

Affiliation:

1. Cardiorenal Research Laboratory, Department of Cardiovascular Medicine, Mayo Clinic, Rochester MN (H.H.C., S.R.I., J.S., J.C.B.).

2. Division of Cardiology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas (S.-H.W.).

3. Department of Internal Medicine, University of Parma, Parma, Italy (V.C.).

4. Integrium, Tustin, CA (J.N.).

Abstract

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.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Internal Medicine

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