Advanced Cell Technology is currently focused on using its proprietary technologies to generate stable cell lines including retinal pigment epithelium (RPE) cells for the treatment of diseases of the eye, including macular degeneration, which represents a $28 billion dollar market. Age-related macular degeneration (AMD) affects more than 30 million people worldwide and is the leading cause of blindness in people over 60 years of age in the United States. AMD is a disorder that affects the macula of the eye that causes decreased visual acuity and possible loss of central vision. The prevalence of AMD begins to increase after the age of 50. Approximately 15% of people over 75 years of age have the condition.
ACT demonstrated the ability to rescue visual function in rats through implantations of RPE cells derived from human embryonic stem cells. In collaboration with Raymond Lund at the University of Utah, the company performed RPE transplantation into sub-retinal space of rats that naturally become blind in several weeks due to RPE degeneration and photoreceptor death. In the experiments conducted by the company, the rats were injected with embryonic stem-RPE cells into the sub-retinal space of the eye at 21 days after their birth — an age at which photoreceptor degeneration has not yet occurred. As control measures, some rats received injections of cell culture medium alone or were not injected at all. Subsequently, tests for visual function were performed at 60 and 90 days after birth — times at which loss of photoreceptor cell has produced characteristic vision deficits. The results represented a major breakthrough. The injected RPE cells grew normally without forming teratomas. Soon, the rats were able to follow lights with their eyes and attained approximately 70% of the spatial acuity of a normal, healthy rat. Necropsy revealed that the eyes had grown layers of the retinal cells. The experiment demonstrated that animals receiving the human embryonic stem cell-derived RPE cells performed significantly better than medium-only treated (50% improvement), or untreated (100% improvement) controls in visual performance. In addition, the human embryonic stem cell-derived RPE cells did not appear to cause any side effects in the animals. The research was published in Cloning and Stem Cells and was also referenced in Scientific American.
Advanced Cell Technology subsequently entered into a sponsored research agreement with Oregon Health and Science University. The company is collaborating with Dr. Raymond Lund, Dr. Richard Weleber and Dr. Peter Francis at the Casey Eye Institute to conduct preclinical studies for its RPE program. Specifically, the research team is conducting a dosage study utilizing the Company’s RPE cells in the Royal College of Surgeons (“RCS”) rat model and plans to conduct similar studies in other rodent models of retinal degenerative disease. The company is also in discussions with the Oregon Health and Science University team in regard to future plans for a Phase I human clinical trial.
Furthermore, after discussions with staff from the Office of Cellular, Tissue, and Gene Therapies within the Center for Biologics Evaluation and Research at the Food and Drug Administration (FDA), ACT contracted with a leading contract research organization to commence work on an extensive preclinical program. Earlier, MPI Research, located in Mattawan, Michigan, initiated pilot studies under Good Laboratory Practices (GLP) for the RPE program. This study was the first of several that will provide substantial safety data for an Investigational New Drug (IND) application, necessary for the initiation of a clinical trial. The protocols utilize therapeutic dosage levels of RPE cells based on recent data obtained through pharmacological dosage studies in the RCS rat, a key animal model of retinal disease. For the preliminary GLP studies, the company is utilizing RPE cells that have been differentiated from human embryonic stem cells, under current Good Manufacturing Practice (cGMP) conditions in its Massachusetts facility. Applying appropriate controls as specified in the FDA’s cGMP regulations, ACT staff was able to produce master and working cell banks of human embryonic stem cells. In working out a controlled, compliant manufacturing methodology, an unlimited amount of RPE cells can be derived by ACT for clinical use. ACT scientists have also developed novel methodology to cryopreserve the RPE cell product, thereby overcoming various clinical issues faced by other cell therapy companies. In early 2008, ACT completed pre-IND meetings with the FDA. The company plans to file an IND for its RPE therapy in 2008.