Preprogrammed Bone Marrow Cells as a Systemic Therapy for Dry AMD
In previous studies, Drs. Michael Boulton, Maria Grant and colleagues made the exciting discovery that changing the expression of one gene in isolated bone marrow‐derived plasma cells (BMPCs)—a type of adult stem cell— transforms them into RPE‐like cells. When these cells are injected back into the blood of mice with physically damaged eyes, they go to the retina, renew the single‐layer of RPE cells, and re‐establish normal vision. Drs. Boulton and Grant plan to test this RPE‐replacement treatment in mice with AMD. If this treatment is proven to be effective in these mice, it could lead to human clinical trials and treatment possibilities without the need for invasive eye surgery or injections.
During the first year of the study, this team has injected genetically-modified BMPCs into the bloodstream of the mice at one and two months after the induction of AMD to study prevention of the disease. They successfully reprogrammed isolated BMPCs in a culture dish by genetically modifying them with the RPE differentiation marker, called RPE65. Systemic delivery of these genetically-modified cells via the tail vein in the mice prevented the progression of early AMD. Introduction of these genetically-modified BMPCs maintained visual function, retained retinal thickness, and prevented degeneration of the retina in AMD mice which was not observed in AMD mice receiving “control” treatments, including being given bone marrow progenitors which were programmed with an irrelevant gene. This team is now evaluating the effect of administering genetically-modified BMPCs at 3 and 6 months after induction of AMD to investigate the best time for treatments. The data obtained in the first year validate Dr. Boulton’s hypothesis and provides an experimental paradigm that could become the basis for cell-based therapies in the clinic for not only AMD but also for retinal degenerative diseases such as Best disease, Stargardt's disease and forms of retinitis pigmentosa.
First published on: July 6, 2011
Last modified on: March 18, 2013