Background

Pulmonary arterial hypertension (PAH) is a rare and fatal cardiopulmonary disease characterized by an elevation of pulmonary artery pressure (PAP) and vascular resistance, which can lead to right ventricular (RV) failure and ultimately death. Currently there is no curative therapy for PAH, while the available therapies, such as endothelin receptor antagonists, prostacyclin analogs, and phosphodiesterase 5 (PDE5) inhibitors have significant limitations. Mount Sinai’s investigators have identified Switch-Independent 3a (SIN3a) is a critical epigenetic regulator in the lung. Data revealed SIN3a expression is significantly reduced in PAH patients and several experimental animal models of pulmonary hypertension (PH).

Technology Overview

Investigators have developed an AAV-mediated delivery of SIN3a as a method to treat PAH. This approach can inhibit the proliferation of pulmonary arterial cell proliferation and has further shown to reverse pulmonary vascular remodeling in animal models of PAH .

Stage of Development

SIN3a overexpression in vitro inhibits human pulmonary artery smooth muscle cells (PASMC) proliferation and migration
Validated in vivo delivery of SIN3a gene therapy
Therapeutic intratracheal delivery of SIN3a reverses PAH phenotype while preserving cardiac function in a monocrotaline rat animal model of PAH.
Reverses lung remodeling in Sugen/ hypoxia mouse model of PAH

Benefits

SIN3a gene therapy approach demonstrates targeting specificity (highly vascular cells-selective)
Restoration of SIN3a levels (via AAV1 gene delivery) can prevent and reverse disease phenotype

Intratracheal Gene Delivery of SIN3A Inhibits Pulmonary Arterial Hypertension

IP Status

Seeking