Friday, April 19, 2024
4/19/2024
PROJECT SUMMARY / ABSTRACT The present administrative supplement application responds to NOT-AG-20-008, “Alzheimer's- focused administrative supplements for NIH grants that are not focused on Alzheimer's disease”. Under the parent grant for the present administrative supplement, R01 grant 1R01EY030747-01, entitled “Novel pro-drug pharmacotherapy to prevent neuronal and cell degeneration in AMD”, we are targeting a novel signaling pathway for the development of a novel pharmacological intervention to control degeneration of retinal pigment epithelial (RPE) and nerve cells in the retina due to Age-related Macular Degeneration (AMD), a major cause of visual loss and blindness in the United States and worldwide. Specifically, we plan to develop a new therapeutic strategy in the multidisciplinary research project of the parent award using established models of human AMD, a novel chemical antioxidant strategy to protect RPE cells and neurons from apoptosis. The research proposed in the present administrative supplement application will allow us to build on these novel preclinical data sets and thereby to develop the novel therapeutic strategy for neurons of the central nervous system (CNS) affected by Alzheimer's disease (AD). Specifically, we will test the hypothesis that similar to RPE cells and retinal neurons affected by AMD, oxidative stress resulting from AD pathology reducing viability and function of CNS neurons can be attenuated by the novel therapeutic strategy under development in the parent award. To this end, a novel intervention approach will be developed that can be exploited to devise novel treatments that can be delivered to CNS neurons affected by AD protecting them from oxidative stress mediated damage and loss of function. Three- dimensional (3D) bio-printed human neural cell constructs will be used as in vitro models for AD and for drug discovery in AD and related dementias employing experimental strategies aligned with the parent award. The proposed experiments will determine the potential of the targeted novel therapeutic strategy for neuroprotective and anti-oxidant therapies in AD. The innovative strategy has the potential to generate a first-in-class pharmacotherapy approach for AD. The strategy's potentially high impact lies in its capacity to be both preventative and therapeutic in nature and to complement current and future treatment designs and rationales.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).
