Antihypertensive Designer Peptide Appears Safe and Effective in First Human Trial

By Rob Goodier

November 24, 2021

NEW YORK (Reuters Health) - The designer peptide MANP met safety and efficacy goals for the treatment of hypertension in its first trial on human patients, researchers report.

"MANP lowered blood pressure, increased urinary sodium excretion and suppressed aldosterone with duration of 24 hours with a single subcutaneous administration," Dr. Horng Chen of Mayo Clinic in Rochester, Minnesota, told Reuters Health by email. "These studies support further investigations to evaluate the efficacy of MANP in lowering blood pressure in patients with resistant hypertension or difficult-to-control hypertension."

MANP, or M-atrial natriuretic peptide, is designed as an enhanced atrial natriuretic peptide that activates particulate guanylyl cyclase (GC-A) receptors and suppresses aldosterone.

For the study, published in Hypertension, Dr. Chen and colleagues recruited 12 patients with hypertension, dividing them into three cohorts of four people. Two weeks prior, the patients washed out their prescribed hypertension medications.

The study increased the dosage with each cohort. The first cohort started treatment at a dosage of 1 ug/kg subcutaneously injected, and the second cohort was dosed at 5 ug/kg. Two people in the second group saw a drop in systolic blood pressure of at least 30 mmHg, which was one of the end points of the study, so the last cohort was dosed less at 2.5 ug/kg.

There were no serious adverse events. Plasma cyclic guanosine monophosphate was activated after the MANP injections and rose in tandem with plasma levels of the peptide, as expected. At all three doses, plasma aldosterone decreased after the MANP injection, and patients excreted sodium in the urine at a rate that increased with the dose of MANP.

Systolic and diastolic blood pressure decreased after treatment in all three groups. The most marked reductions occurred 2-12 hours after injection.

"I am very impressed with the potential for MANP to be effective in lowering BP and protecting target organs in hypertensive patients, particularly treatment resistant hypertension. This is because it has multiple actions (including) natriuresis, vasodilation and renin-angiotensin-system suppression," said Dr. Suzanne Oparil, a professor of medicine and director of the Vascular Biology and Hypertension Program at the University of Alabama at Birmingham, who was not involved in the research.

"Many patients with resistant hypertension require 5 or 6 drugs to effectively lower their BP," she told Reuters Health by email. "MANP has the potential to simplify their treatment. Of course, much more data are needed, particularly in patients with hypertension that is uncontrolled on multi-drug regimens."

The study was partly funded by Broadview Ventures. The Mayo Clinic has licensed MANP to E-STAR BIO TECH. One of Dr. Chen's coauthors is the inventor of MANP.

SOURCE: Hypertension, online October 18, 2021.