# Advancing treatment and molecular understanding of oculocutaneous albinism through gene therapy

> **NIH NIH F30** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $51,930

## Abstract

Project Summary/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 scienti...

## Key facts

- **NIH application ID:** 10899862
- **Project number:** 1F30EY036249-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Alessandra Larimer-Picciani
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $51,930
- **Award type:** 1
- **Project period:** 2024-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899862

## Citation

> US National Institutes of Health, RePORTER application 10899862, Advancing treatment and molecular understanding of oculocutaneous albinism through gene therapy (1F30EY036249-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10899862. Licensed CC0.

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