The Regenerative Medicine for EB and Related Diseases at Stanford (REMEDIS) Center
Abstract
Overall Program The REgenerative Medicine for EB and related DIseases at Stanford (REMEDIS, pronounced remedies) Center focuses on curing the incurable, the genetic disease, Epidermolysis Bullosa (EB), a topic area of the FY21 PRMRP Area of Encouragement. Patients with the severe generalized variant of EB, Recessive Dystrophic EB (RDEB, prevalence of 1 in 250,000), have a defect in the gene encoding the basement membrane zone protein type VII collagen (COL7A1 gene). Type VII collagen plays a crucial role in the adherence of the stratified epithelium to the body and with chronic wounding, RDEB patients are at high risk for dying from invasive skin cancer by age 40. No approved therapy currently exists. Correction of the mutation within tissue stem cells would provide a permanent corrective therapy for RDEB and previous work by our group and others indicates that type VII collagen-expressing epithelial stem cells does indeed possess powerful, long-term disease modifying activity. The advent of CRISPR-correction and induced pluripotent cell (iPS) stem cell technologies has brought the possibility of producing large-scale quantities of genetically corrected skin and esophagus stem cells that can heal the wounds of the RDEB patients. While we have made enormous progress toward submitting U.S. Food and Drug Administration (FDA) packages for each of these cell therapies, several key hurdles prevent further efficient clinical development and addressing these hurdles is the focus of this proposal. The overarching hypothesis of the REMEDIS Center posits that hurdles preventing effective clinical development of EB therapies can be overcome by coordinating the creation, manufacturing, and delivery of corrected IPS cell-based therapies with the intimate and interactive clinical care of EB patients. The REMEDIS team is composed of experts with over 30 years of experience that have worked together for 12 years in the clinical care of EB patients, in skin biology, and clinical translation of the first gene-therapy product for healing RDEB skin wounds. The Focused Project consists of five synergistic, but independent research projects that will each tackle a particular key hurdle hampering the launch of first-in-human Proof of Concept (POC) EB clinical trials and thus is compliant with FY21 PRMRP Focused Program Award criteria. Importantly, as described below, none of the projects rely on the success of the other projects as they aim to improve independent steps in a cell manufacturing, regulation, or delivery process that already exists. By contrast, the success of each project will inform and synergize with the successes of the other projects. REMEDIS Center project success will allow the development of a more universal platform for CRISPR correction and manufacturing of collagen VII producing tissue stem cells, and a model for at-home patient registry creation that will accelerate the development and testing of cell-based therapies for RDEB patients. Long-term impacts of REMEDIS Center project success include developing cell-based cures for previously incurable genetic diseases and the development of a flexible manufacturing platform to produce cell-based regenerative medicine therapies for other tissues. A key long-term impact is the potential application of autologous iPSC-derived skin stem cells for the treatment of acute or chronic wounds in military personnel and Veterans. The REMEDIS Center proposal aligns with the Armed Forces Institute of Regenerative Medicine’s Skin Repair Program, which addresses the clinical challenges of wounds and skin replacement by using new technologies in regenerative medicine and tissue engineering (i.e., the novel use of cells, scaffolds and biomaterials) to provide surgeons with advanced tools and new options for repair, regeneration, and restoration of skin and soft tissue in injuries. Advances in manufacturing and delivery of tissue stem cells make it possible to deliver them to the partic
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210272
Entities
People
- Anthony Oro
Organizations
- Stanford University
- United States Army