Special Commentary: Early Clinical Development of Cell Replacement Therapy: Considerations for the National Eye Institute Audacious Goals Initiative

Abstract

The National Eye Institute (NEI) launched the Audacious Goals Initiative (AGI) in 2013 with the aim “to restore vision through the regeneration of neurons and neural connections in the eye and visual system.” An AGI Town Hall held at the Association for Research in Vision and Ophthalmology Annual Meeting in 2016 brought together basic, translational, and clinical scientists to address the clinical implications of the AGI, with a particular emphasis on diseases amenable to regenerative medicine and strategies to deal with barriers to progess. An example of such a barrier is that replacement of lost neurons may be insufficient because damage to other neurons and non-neuronal cells is common in retinal and optic nerve disease. Reparative processes such as gliosis and fibrosis also can make it difficult to replenish and regenerate neurons. Other issues include choice of animal models, selecting appropriate endpoints, ethics of informed consent, and regulatory issues, Another area critical to next steps in the AGI is the choice of target diseases and the stage at which early development studies should be focused. For example, an advantage of doing clinical trials in patients with early disease is that supporting cellular and structural constituents are still likely to be present. On the other hand, regenerative studies in patients with late disease make it easier to detect the effects of replacement therapy against the background of severe visual loss, while it may be harder to detect incremental improvement in visual function in those with early disease and considerable remaining visual function. Achieving the goals of the AGI also requires preclinical advances, new imaging techniques, and optimizing translational issues. The work of the AGI is expected to take at least ten years, but should eventually result in therapies to restore some degree of vision to the blind.

Characterization of lincRNA expression in the human retinal pigment epithelium and differentiated induced pluripotent stem cells

“…For example, previous studies used iPS-RPE to model the retinal dystrophies Best vitelliform macular dystrophy and age-related macular degeneration [ 37 ]. This is providing a more streamlined pipeline for determining the mechanism of disease pathogenesis, which should aid the development of therapeutic strategies, such as gene therapy or cell replacement therapy [ 38 – 40 ].…”

Implementation of experimental cellular (cellular-genetic) therapies on the example of eye diseases

“…Currently the research is in phase I/II. The most important focus is on regenerative photoreceptor therapies in AMD and hereditary retinal dystrophies (RP and Stargardt disease) [49,50]. Moreover, in view of recent developments, the aim is to use CD34+ cells isolated from the bone marrow to treat vision loss due to various retinal disorders.…”

Mechanisms Underlying the Visual Benefit of Cell Transplantation for the Treatment of Retinal Degenerations

“…These animal studies are proof of concept for human clinical trials [79,15]. RPE transplantation has to overcome the immune rejection despite the existence of ocular immune privilege.…”