Development of Orally Bioavailable Therapeutics by the Chloroplast Expression System to Counter Muscle Degeneration, Weakness, and Fibrosis in DMD
Abstract
Patients with DMD suffer from progressive muscle weakness and damage, resulting in fibrotic replacement. The goal of this project is to evaluate the therapeutic potential of the anti-fibrotic agents, ACE2/Ang(1-7), when produced in plants using a chloroplast expression system. Lyophilized plant material was delivered by oral gavage to the mdx mouse model for DMD. Initial studies were done to ensure that the plant material and protein was orally bioavailable. Further, additional studies confirmed that ACE2 protein accumulated in the circulation over the course of the treatment. Functional assessment of mice treated for 2 weeks showed improved strength in the diaphragm and EDL muscles. However, by 2 months of treatment the benefits were reduced back to untreated controls. This lack of long-term benefit was not due to compound delivery, which accumulated in the circulation over the course of the study. Instead, we believe that the muscle tissue compensated by down regulating the receptors that are sensitive to the heightened Ang(1-7)levels. Even though this therapeutic agent did not provide benefit, we assert that this delivery strategy may provide a new way to introduce therapeutic proteins for treating neuromuscular disease.
Document Details
- Document Type
- Technical Report
- Publication Date
- Feb 01, 2018
- Accession Number
- AD1059201
Entities
People
- Elisabeth Barton
Organizations
- University of Florida