The purpose of this program is to accelerate the development of tools and/or novel therapies, devices, or other resources that will serve as a resource to clinicians for the treatment of visual system diseases and disorders. The reissue of the FOA has been expanded to include medical devices and assistive technologies. In the context of this program, an expert develops a multi-disciplinary research team that employs an integrative approach to the rapid and efficient translation of innovative laboratory research findings into clinical therapeutic development. It involves collaborative teams of scientists and clinicians with expertise in multiple disciplines, operating according to a clear leadership plan. Such a collaborative approach is particularly appropriate for research focused on pathways that will likely be targeted by biological intervention, such as gene therapy, cell-based therapy, pharmacological approaches, and devices. The intention of this program is to make resources available to clinicians for the treatment of visual system disorders. This program is not intended to expand solely basic science discoveries nor to support isolated technology development.
Each project should have a well-defined end point, achievable within a five-year time frame, of developing a new device or treatment for a specific ocular disease. The steps towards this goal should be clearly delineated in a series of milestones that support the development of a therapeutic or device that can be tested in a clinical trial. Projects funded under this FOA may not propose human clinical trials. If successful, a project funded under this program should lead to filing an IND-directed pharmacological and toxicological study, Phase I clinical testing and a subsequent application for a NEI Clinical Vision Research Grant (UG1) or a Clinical Study Development Grant (R34).
The objective of this FOA is to encourage collaborative research that facilitates the translation of focused laboratory and animal studies into novel resources for the treatment of ocular diseases. Translational research may target new or previously identified genes, molecules, and/or pathways that are deemed to be appropriate for therapeutic intervention.
The scope of this program is broad; it is intended to cover all visual system diseases and disorders that are relevant to the mission of the NEI. The concept is to bring teams of experts together to create a pipeline for therapy development and medical devices for disease treatment. It is expected that the application will have a well-defined goal that will be achieved within the project period. The scope of the proposed research should be beyond the capabilities and resources of one research laboratory. For example, gene therapy may require research teams able to contribute resources such as therapeutic genes, cells and vectors capable of appropriate tissue targeting and gene expression, animal models for toxicology and efficacy testing, and clinical expertise. Rational drug design may require different scientific disciplines to identify and validate appropriate therapeutic targets, devise suitable delivery systems, and test the efficacy and safety of such agents in animal models.
The suggested topics such as gene therapy, selectively targeted cell-based therapy, stem cell therapy, and small molecule based therapy are presented as general examples, and are not intended to be exclusive nor to limit creativity and innovation:
- Gene transfer: Considerable progress has been made in vector design, and therapeutic strategies are emerging. Gene therapy is most likely to reach clinical importance in monogenic disease where the replacement of one mutated gene may be curative (such as juvenile glaucoma, macular corneal dystrophy, retinitis pigmentosa, pseudoxanthoma elasticum, juvenile cataract) or in pathological conditions which require a temporary expression of a transferred gene (such as a growth factor or ribozyme) to achieve a beneficial clinical effect.
- Selectively targeted cell-based therapies: Cells expressing various angiostatic or neurotrophic factors might represent another approach. Autologous grafts of such cells alone or after transfection to express a desirable gene product would avoid some of the immunological problems associated with viral vectors. Expression of trophic factors might achieve generic rescue effects on selected cell populations, possibly circumventing the need to target specific gene defects.
- Stem cell therapy: Human adult bone-marrow-derived stem cells, and iPS cells appear to have stabilizing effects on retinal blood vessel loss in animal models of retinal degeneration.
- Rational drug design: Characterization of pathways leading to cell degeneration and death could provide target points for therapeutic intervention in retinal diseases such as glaucoma and age-related macular degeneration. Conversely, the identification of factors that enhance cell survival may protect against such degeneration. The development of neuroprotection strategies to arrest or halt the degenerative process, or stimulate the regeneration of damaged tissue would benefit from a multidisciplinary research approach.
- Small molecules: Specifically, those small molecule compounds that show promise for treating visual disorders, but are not yet suitable for clinical testing for ocular diseases. These small molecules may result in development of neuroprotection strategies to arrest or halt the degenerative disease process.
- Prosthesis and other devices: Medical Devices may include sensory substitution, disease treatment, and assistive technologies. For example, degenerative retinal diseases (e.g., retinitis pigmentosa) may be treated by implantation of retinal prosthetics, to substitute for the lost photoreceptors. The prosthetic transforms light to electrical signals that stimulate the remaining retinal neurons that are then perceived by the patient as visual percepts. Devices to deliver therapeutic agents to eye tissue are an important means to treat eye diseases to provide symptomatic relief and/or mechanistic reversal of eye diseases. Such devices can offer localized delivery of agents, ranging from genes to low-intensity light. Assistive technologies can aid people with low-vision or blindness with their everyday activities of life. Indoor wayfinding, street crossing, and graphical information access are representative of important tasks necessary for independent living. Inexpensive, reliable technology to create refreshable Braille displays would make a major positive impact on the lives of people with low vision or blindness.
Deadlines: March 27, 2017; March 27, 2018; March 27, 2019
Filed Under: Funding Opportunities