A PHASE 2, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, DOSE TITRATION, MULTI-CENTER STUDY TO EVALUATE THE SAFETY AND EFFICACY OF SUBCUTANEOUS MANP WHEN ADMINISTERED ONCE DAILY FOR 42 DAYS IN PARTICIPANTS WITH DIFFICULT TO CONTROL HYPERTENSION/RESISTANT HYPERTENSION

This is a Phase 2 dose-titration study designed to evaluate the safety and efficacy of MANP subcutaneous injection compared to placebo in reducing baseline daytime systolic blood pressure (SBP), derived from 24-hour ambulatory blood pressure monitoring (ABPM), in subjects with hypertension who are taking 3 or more antihypertensive medications with different mechanisms of action.

Start Date17 Nov 2024

Sponsor / Collaborator

E-Star BioTech, LLC

[+3]

NCT05279742

/ Enrolling by invitationPhase 1/2IIT

Enhancing the Natriuretic Peptide System in HFpEF: a Randomized Double-Blind Placebo-Controlled Triple Crossover Study

The purpose of this study is to look at the differences in how individuals with heart failure with preserved ejection fraction in the presence of chronic kidney disease (HFpEF-CKD) and exercise induced dyspnea without objective findings of fluid retention (HFpEF-EI) bodies function using drugs Sacubatril/Valsartan (Entresto) and MANP.

Start Date04 Nov 2022

Sponsor / Collaborator

Mayo Clinic

NCT05247528

/ CompletedPhase 1

A Phase 1B, Multiple Ascending Dose Trial Examining The Safety And Tolerability Of Subcutaneous MANP In Difficult To Control/Resistant Hypertensive Subjects

A randomized, double-blind, placebo-controlled multiple ascending dose study in hypertensive subjects on stable doses of at least three hypertensive drugs for at least 6 weeks prior to Screening. The study will consist of screening, PK-unit admittance, and safety follow up periods.
Subjects will be randomized at a 6:2 ratio of either MANP or placebo and will be stratified by race in each dosage cohort. The entire first Cohort will be given the lowest dosage with subsequent cohorts progressing sequentially to the higher doses depending on safety and tolerability of the previous cohort.
Endpoints not related to the safety reviews will be analyzed after the last patient last visit (LPLV).

Start Date20 Dec 2021

Sponsor / Collaborator

E-Star BioTech, LLC

[+2]

100 Clinical Results associated with SA-ANP

100 Translational Medicine associated with SA-ANP

100 Patents (Medical) associated with SA-ANP

Literatures (Medical) associated with SA-ANP

10 Mar 2025·European Heart Journal Open

Inhibiting atrial natriuretic peptide clearance reduces myocardial fibrosis and improves cardiac function in diabetic rats

Article

Author: Bakhos, Jules Joel ; Saliba, Youakim ; Oskaridjian, Hrag ; Achkouty, Guy ; Semaan, Albert ; Hatem, Stéphane N ; Hajal, Joelle ; Azevedo, Chloé ; Albuquerque, Miguel ; Balse, Elise ; Fares, Nassim ; Suffee, Nadine

AbstractAimsNatriuretic peptides (NPs) exert pleiotropic effects through the recruitment of cyclic guanosine monophosphate (cGMP) signalling pathways depending on their bioavailability, which is regulated by clearance receptors and peptidases. Here, we tested the hypothesis that increasing myocardial bioavailability of NP has a beneficial effect on heart failure. We studied the effects of a mutated NP, M-atrial natriuretic peptide (MANP), resistant to neprilysin in a model of diabetic cardiomyopathy characterized by marked myocardial fibrosis.Methods and resultsNatriuretic peptides as well as sacubitril were delivered via osmotic mini-pumps to high-fat/streptozotocin-induced Type 2 diabetic (T2D) rats. Cardiac function was evaluated by echocardiography. Myocardial remodelling was studied by histological approaches, collagen phenotype, and atrial natriuretic peptide (ANP)/cGMP concentrations. Live-cell cGMP biosensing was conducted on cultured rat cardiac fibroblasts to investigate the biological effects of NP. Cyclic guanosine monophosphate signalling pathway was studied using multiple antibody arrays and biochemical assays in cardiac tissue and cultured fibroblasts. M-atrial natriuretic peptide exhibits superior efficacy than ANP in reducing left ventricular dysfunction and myocardial fibrosis with less extracellular matrix deposition. In vitro, MANP and ANP similarly generated cGMP and activated the protein kinase G (PKG) signalling pathway in cardiac fibroblasts, attenuating Mothers against decapentaplegic homolog 2 (SMAD) activation, collagen secretion, and cell proliferation. Nevertheless, in vivo, MANP specifically enhanced cardiac cGMP accumulation and was more potent than ANP in activating myocardial cGMP/PKG signalling and inhibiting the profibrotic SMAD, extracellular signal-regulated kinases 1/2, and nuclear factor of activated T cells 3 pathways. Endopeptidase inhibition using sacubitril also led to cardiac ANP/cGMP accumulation and reduced myocardial fibrosis.ConclusionMyocardial bioavailability of ANP is a major determinant of peptide efficacy in reducing cardiac fibrosis and improving pump function during diabetic cardiomyopathy.

01 Jan 2023·Frontiers in chemistry

Green synthesis of MgO nanoparticles and its antibacterial properties.

Article

Author: Ashgar, Sami S. ; Manjunath, Ramya ; Babalghith, Ahmad O. ; Rotti, Rajeshwari B. ; Abdulaziz, Osama ; Mayegowda, Shilpa Borehalli ; Gnanaprakash, A. P. ; Allahyani, Mamdouh ; Alghamdi, Saad ; El-Lateef, Amal Ezzat Abd ; Sunitha, D. V. ; Alsaiari, Ahad Amer ; Roy, Arpita ; Khidir, Elshiekh B. ; Almehmadi, Mazen ; Aljuaid, Abdulelah

Magnesium oxide nanostructured particles (NP) were prepared using a simple solution combustion technique using different leaf extracts such as Mangifera indica (Mango - Ma), Azadirachta indica (Neem-Ne), and Carica papaya (Papaya-Pa) as surfactants. The highly crystalline phase of MgO nanostructures was confirmed by PXRD and FTIR studies for 2 h 500°C calcined samples. To analyze the characteristics of obtained material-MaNP, NeNP, and PaNP for dosimetry applications, thermoluminescence (TL) studies were carried out for Co-60 gamma rays irradiated samples in the dose range 10-50 KGy; PaNP and NeNP exhibited well-defined glow curve when compared with MaNP samples. In addition, it was observed that the TL intensity decreases, with increase in gamma dose and the glow peak temperature is shifted towards the higher temperature with the increase in heating rate. The glow peak was segregated using glow curve deconvolution and thermal cleaning method. Kinetic parameters estimated using Chen's method, trap depth (E), and frequency factor (s) were found to be 0.699, 7.408, 0.4929, and 38.71, 11.008, and 10.71 for PaNP, NeNP, and MaNP respectively. The well-resolved glow curve, good linear behavior in the dose range of 10-50, KGy, and less fading were observed in PaNP as compared with MaNP and NeNP. Further, the antibacterial activity was checked against human pathogens such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. A visible zone of clearance was observed at 200 and 100 μg/mL by the PaNP and NeNP, indicating the death of colonies by the nanoparticles. Therefore, PaNP nanomaterial is a potential phosphor material for dosimetry and antibacterial application compared to NeNP and MaNP.

01 Aug 2022·Hypertension

MANP Activation Of The cGMP Inhibits Aldosterone Via PDE2 And CYP11B2 In H295R Cells And In Mice

Article

Author: Pellegrini, Manuela ; Burnett, John C. ; Naro, Fabio ; Nikolaev, Viacheslav O. ; Chen, Yang ; Cardarelli, Silvia ; Lee, Hon-Chi ; Ma, Xiao ; Iyer, Seethalakshmi R.

Background:Aldosterone is a critical pathological driver for cardiac and renal diseases. We recently discovered that mutant atrial natriuretic peptide (MANP), a novel atrial natriuretic peptide (ANP) analog, possessed more potent aldosterone inhibitory action than ANP in vivo. MANP and natriuretic peptide (NP)-augmenting therapy sacubitril/valsartan are under investigations for human hypertension treatment. Understanding the elusive mechanism of aldosterone inhibition by NPs remains to be a priority. Conflicting results were reported on the roles of the pGC-A (particulate guanylyl cyclase A receptor) and NP clearance receptor in aldosterone inhibition. Furthermore, the function of PKG (protein kinase G) and PDEs (phosphodiesterases) on aldosterone regulation are not clear.Methods:In the present study, we investigated the molecular mechanism of aldosterone regulation in a human adrenocortical cell line H295R and in mice.Results:We first provided evidence to show that pGC-A, not NP clearance receptor, mediates aldosterone inhibition. Next, we confirmed that MANP inhibits aldosterone via PDE2 (phosphodiesterase 2) not PKG, with specific agonists, antagonists, siRNA silencing, and fluorescence resonance energy transfer experiments. Further, the inhibitory effect is mediated by a reduction of intracellular Ca2+ levels. We then illustrated that MANP directly reduces aldosterone synthase CYP11B2 (cytochrome p450 family 11 subfamily b member 2) expression via PDE2. Last, in PDE2 knockout mice, consistent with in vitro findings, embryonic adrenal CYP11B2 is markedly increased.Conclusions:Our results innovatively explore and expand the NP/pGC-A/3',5', cyclic guanosine monophosphate (cGMP)/PDE2 pathway for aldosterone inhibition by MANP in vitro and in vivo. In addition, our data also support the development of MANP as a novel ANP analog drug for aldosterone excess treatment.

100 Deals associated with SA-ANP

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Resistant hypertension	Phase 2	United States	Mayo Clinic	17 Nov 2024
Chronic Kidney Diseases	Phase 2	United States	Mayo Clinic	04 Nov 2022
Heart failure with normal ejection fraction	Phase 2	United States	Mayo Clinic	04 Nov 2022

Clinical Result

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


ESC2024	Phase 1	Resistant hypertension	36	MANP	vyrahalkwn(uvopvonwfj) = There were no reported drug related serious adverse events vsjcghnyeb (nwjwjopigd ) View more	Positive	30 Aug 2024
				Placebo
NCT03781739 (ESC2023)	Phase 1	Metabolic Syndrome \| Hypertension	22	MANP	smoymzjlwh(knwsdosqcq) = rfikgpquwu essxfhlsht (bivhwdgjyy ) View more	-	26 Aug 2023
ESC2016	Phase 1	Hypertension	-	ZD100	aouwtfupth(opcbrwxylb) = ixvflmhcfj okflfnprwz (znchyudtof ) View more	-	28 Aug 2016
				Placebo	wyzcrakryh(wzhuogyhoa) = mjoopcvuhi wxizyulpaf (friztbgwqz ) View more

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