# Intravenous MitoTargeted AAV9 Gene Therapy for Treatment of Visual Loss and Encephalopathy in Leigh Syndrome and NARP

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $383,750

## Abstract

Mutations in mitochondrial DNA lead to a spectrum of neurodegenerative diseases for which no
effective treatment exists. This is a group of untreatable disorders affecting the eye, nervous
system and heart, some clinically characterized over a century ago, but they are now known to
be a spectrum of molecularly defined diseases. We had chosen to start with one of the most
severe, the ATP6 mutation (T8993G) in mitochondrial (mt) DNA responsible for Maternally
Inherited Leigh Syndrome (MILS), a neurologic disease renowned for causing blindness and
rapidly fatal encephalomyelopathy in early childhood or Neurogenic Ataxia and Retinitis
Pigmentosa in early adulthood.
We have made major strides towards determining the pathogenesis and testing treatments for
another common mitochondrial disorder Leber hereditary optic neuropathy (LHON). In this
application, we propose to design, modify and test the efficacy and safety of a clinically relevant
vector for the treatment of MILS and NARP caused by mutated ATP6. Our Aims are: (1) To
facilitate translational studies for MILS and NARP by developing an MTS AAV serotype 9 vector
for intravenous use to deliver the normal ATP6 gene directly to the mitochondria and test
expression to rescue respiration in cybrid cells with 100% mutated T8993G mitochondrial DNA.
(2) To evaluate biological effects of intravenous delivery of MTS AAV9 vectors in normal mice
that result in mitochondrial gene transfer without adverse effects.(3) To rescue visual loss,
encephalomyelopathy and death in transgenic ATP6 mice. We hope to identify the conditions
for long-term rescue of visual loss and encephalomyelopathy in mice, so that this approach can
be tested in a phase I/II clinical designed to restore visual and neurologic function in MILS and
NARP patients.

## Key facts

- **NIH application ID:** 9893880
- **Project number:** 5R01EY027414-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Hong Yu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $383,750
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9893880

## Citation

> US National Institutes of Health, RePORTER application 9893880, Intravenous MitoTargeted AAV9 Gene Therapy for Treatment of Visual Loss and Encephalopathy in Leigh Syndrome and NARP (5R01EY027414-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9893880. Licensed CC0.

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