Autologous MPO Knock-Out Hematopoietic Stem and Progenitor Cells for Pulmonary Arterial Hypertension
Grant Award Details
Grant Type:
Grant Number:
TRAN1-13345
Investigator(s):
Disease Focus:
Human Stem Cell Use:
Cell Line Generation:
Award Value:
$4,751,297
Status:
Active
Progress Reports
Reporting Period:
Final Operational Milestone #6
Grant Application Details
Application Title:
Autologous MPO Knock-Out Hematopoietic Stem and Progenitor Cells for Pulmonary Arterial Hypertension
Public Abstract:
Translational Candidate
Autologous MPO Knock-Out Hematopoietic Stem and Progenitor Cells
Area of Impact
Pulmonary Arterial Hypertension (PAH), initially associated with Scleroderma (Systemic Sclerosis -SSC), and then applied to other causes of PAH
Mechanism of Action
Myeloperoxidase (MPO) protein produced by neutrophils plays a critical role in the development of PAH. Disrupting the MPO gene in autologous hematopoietic stem and progenitor cells (HSPC) followed by transplantation of the edited HSPC eliminates the source of neutrophil MPO. This approach prevents development of PAH in murine models and, we propose, in patients with PAH in Scleroderma (Systemic Sclerosis-SSc) and other forms of PAH.
Unmet Medical Need
Pulmonary Arterial Hypertension (PAH) is a progressive condition for which there is no cure; existing treatments provide only symptomatic relief and survival remains unacceptably poor. Transplantation of autologous hematopoietic stem cells with MPO gene knock-out may be a novel treatment for PAH
Project Objective
Pre-IND meeting
Major Proposed Activities
Autologous MPO Knock-Out Hematopoietic Stem and Progenitor Cells
Area of Impact
Pulmonary Arterial Hypertension (PAH), initially associated with Scleroderma (Systemic Sclerosis -SSC), and then applied to other causes of PAH
Mechanism of Action
Myeloperoxidase (MPO) protein produced by neutrophils plays a critical role in the development of PAH. Disrupting the MPO gene in autologous hematopoietic stem and progenitor cells (HSPC) followed by transplantation of the edited HSPC eliminates the source of neutrophil MPO. This approach prevents development of PAH in murine models and, we propose, in patients with PAH in Scleroderma (Systemic Sclerosis-SSc) and other forms of PAH.
Unmet Medical Need
Pulmonary Arterial Hypertension (PAH) is a progressive condition for which there is no cure; existing treatments provide only symptomatic relief and survival remains unacceptably poor. Transplantation of autologous hematopoietic stem cells with MPO gene knock-out may be a novel treatment for PAH
Project Objective
Pre-IND meeting
Major Proposed Activities
- Assess PAH disease-modifying activity and safety of transplanted myeloperoxidase (MPO) gene knock-out HSPC
- Develop cGMP cell manufacturing methods and analytic assays for MPO gene knock-out HSPC
- Complete draft of clinical protocol and conduct pre-IND meeting with FDA
Statement of Benefit to California:
Pulmonary Arterial Hypertension (PAH) is a progressive condition for which there is no cure. We are developing a treatment for PAH by transplanting autologous HSC with MPO gene knock-out. The goal is to advance this novel therapy to clinical trials for PAH associated with Scleroderma, an auto-immune disorder often complicated by PAH. Scientific findings and biomedical materials produced from the studies will be publicly available to non-profit and academic organizations in California.
