Advancing treatment and molecular understanding of oculocutaneous albinism through gene therapy
Active Project Grant Awarded Last action
- Award ID
- F30EY036249
- Recipient
-
University Of Pittsburgh - Of The Commonwealth System Of Higher Education UEI MKAGLD59JRL1
- Awarding agency
-
National Eye Institute
National Institutes of Health, Department of Health and Human Services
- Obligated
- $209,424
Award facts
- Assistance listing
- 93.867 Vision Research
- Completion date 51% complete
- Place of performance
- Pittsburgh, PA 15222, USA
Award details come from USAspending.gov.
Description
- Abstract
- Oculocutaneous albinism type 1 (OCA1) is an inherited condition characterized by reduced or absent tyrosinase (TYR) function which leads to a lack of pigment in the hair, skin, and eyes. OCA1 results in debilitating ocular effects, including blindness, severe photosensitivity, and nystagmus. Lack of retinal pigment epithelial (RPE) pigmentation and TYR mutations also lead to developmental anomalies of the neural retina, including foveal hypoplasia and misrouting of retinal ganglion cells (rgcs). OCA1 affects approximately 1 in 40,000 individuals worldwide. Currently, there are no effective treatments to reverse the ocular manifestations of OCA1, making OCA1 therapies a critical unmet clinical need. Moreover, the molecular mechanisms linking TYR mutations and retinal malformation are incompletely understood. This proposal aims to bridge the gaps in both clinical and scientific knowledge by leveraging state-of-the-art adeno-associated viral vector (AAV) gene therapies. OCA1 is a prime disease candidate to benefit from AAV gene therapy as one functional copy of TYR is sufficient to restore pigment production. In addition, gene replacement will serve as a tool to elucidate molecular mechanisms of OCA1 retinal disease. To facilitate the development of AAV-TYR gene therapy for clinical application and to shed light on the molecular underpinnings of ipsilateral RGC mapping in OCA1, we will (1) identify the optimal therapeutic window and delivery route of AAV-TYR, (2) administer our novel AAV-TYR vectors at critical time points in retinal development to rescue ipsilateral RGC fate mapping, and (3) evaluate AAV-TYR using a non- human primate model which closely recapitulates human ocular structure and function. We will accomplish our aims by assessing phenotypic rescue following AAV-TYR delivery at numerous time points in development through ocular imaging and functional testing in a mouse model of OCA1. Further, we will correlate ipsilateral RGC rescue with transcriptomic changes in various cell types within the developing retina through single cell RNA-sequencing. Finally, we will test biocompatibility and safety of AAV-TYR therapy in wildtype rhesus macaques, setting the stage for future testing in an OCA1-NHP model. The experiments described in this proposal will lay the groundwork for developing an OCA1 gene therapy that improves vision and quality of life for patients with OCA1 while also expanding our understanding of OCA1 disease mechanisms. Completion of this proposal will result in a rigorous intellectual and technical training experience under the mentorship of an interdisciplinary team of expert scientists and physicians. The training to be received through this proposal will allow the applicant to accomplish their ultimate goal of becoming an independent physician-scientist investigator with specialization in the treatment of inherited ocular diseases. In SUM, this proposal will result in tangible clinical and scientific benefits in addition to providing an avenue for comprehensive academic and professional development.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $53,070 | |
| Amendment | $52,494 | |
| Amendment | $51,930 | |
| Amendment | $0 | |
| Original award | $51,930 |
Quick answers
Who received award F30EY036249?
F30EY036249 was awarded to University Of Pittsburgh - Of The Commonwealth System Of Higher Education by National Eye Institute (National Institutes of Health) on January 29, 2025.
How much is award F30EY036249 worth?
$209,424 has been obligated on F30EY036249.
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