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Novel Nanomedicine for Treatment-resistant Hypertension (RHTN)

Award Number: R43HL137496
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 03/01/2017
PERIOD OF PERFORMANCE END DATE: 02/28/2018

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Novel Nanomedicine for Treatment-resistant Hypertension (RHTN) - Summary Treatment-resistant hypertension (RHTN) was defined as persistent elevation of blood pressure above goal despite concurrent use of 3 antihypertensive agents, each of unique class with a diuretic included among the treatment regimen, and with all drugs at target dose. RHTN occurs in a fifth of patients with either at least three atherosclerotic risk factors or established disease, and 10% of these patients are refractory to hypertensive treatment even after treatment with 5-6 different classes of antihypertensive drug. RHTN is characterized by uncontrolled hemodynamic changes and vascular dysfunction, and is correlated with a variety of coronary artery disease risk factors. Despite major advances in the treatment of coronary and vascular diseases in the last three decades, physicians are having difficulties to achieve controlled blood pressure in RHTN patients, perhaps due to the lack of therapeutics that can actively improve endothelial functions. As a result, hypertension is unchecked and continues to damage vascular functions every day in millions of RHTN patients, and these patients have a significantly increased risk of all-cause mortality and cardiovascular mortality when compared with those with controlled hypertension. Clearly, novel strategies that can actively improve vascular functions in RHTN patients are much needed. Recent advances have shown that the signaling of a group of vascular receptors, CLR/RAMP receptors, and their cognate ligands (i.e., adrenomedullin [ADM], calcitonin gene-related peptides [a- and ß-CGRP] and intermedin/adrenomedullin 2 [IMD/ADM2]) is essential for vascular development during embryogenesis and throughout adulthood. Consistently, these peptide hormones have been shown to improve angiogenesis, vasculogenesis and endothelial barrier functions in animals, and prevent hemodynamic disturbances in humans. Importantly, we have recently developed a group of peptidomimetics that exhibit superior bioactivity when compared to native ligands. Based on this novel finding, here we propose to develop a poly(DL-lactic-co- glycolic acid)(PLGA)-based superagonist nanoparticle for improving vascular compliance, endothelial integrity, and vasotone in RHTN patients. In this proof-of-concept study, we will identify an optimal nanoparticle formulation for the slow-release of the selected drug candidate in Aim 1. In Aim 2, we will investigate the efficacies of the formulated superagonist nanoparticle in reducing hypertension and cardiac hypertrophy in spontaneous hypertensive rats. Successful completion of this Phase I SBIR proposal will provide us novel drug candidates that are ready for formal preclinical development.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2018 ( Subtotal = $0 )
2018	2017	ADEPTHERA LLC	3353 ALMA ST SUITE245	PALO ALTO	CA	94306	SANTA CLARA	USA	Cardiovascular Diseases Research	000	1	7/2/2018	NEW	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $296,941 )
2017	2017	ADEPTHERA LLC	3353 ALMA ST SUITE245	PALO ALTO	CA	94306	SANTA CLARA	USA	Cardiovascular Diseases Research	000	1	3/1/2017	NEW	$296,941
														Subtotal = $296,941

Grand Total All Awards = $296,941

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Novel Nanomedicine for Treatment-resistant Hypertension (RHTN)

Award Number: R43HL137496

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 03/01/2017

PERIOD OF PERFORMANCE END DATE: 02/28/2018

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