# Translational Gene Therapy for CNGB1 Retinitis Pigmentosa

> **NIH NIH R24** · MICHIGAN STATE UNIVERSITY · 2020 · $1,832,126

## Abstract

Currently there is no treatment for autosomal recessive retinitis pigmentosa (arRP) due to mutations in rod
photoreceptor genes. This multi-investigator, multi-center research project will fill this gap by optimizing
recombinant adeno-associated virus (rAAV) vector gene augmentation therapy for cyclic nucleotide-gated
channel beta 1 (CNGB1) linked RP. The optimized vector will be taken through the stages needed for an
investigational new drug (IND) submission in preparation for a future phase I/II clinical trial. The collaborative
team has expertise in rAAV vector development and production, preclinical and clinical trials for retinal
dystrophies, clinical assessment and recruitment of arRP patients, CNG channel physiology and small and
large animal proof-of-concept gene therapy studies. There are compelling reasons to select CNGB1-RP to fill
this unmet need. First, CNGB1 mutations cause a loss of rod function, but only a slow loss of rods, meaning
there is a wide window of opportunity for intervention while there are still remaining rods. Second, there are
well characterized small (mouse) and large (dog) animal models of CNGB1-RP that recapitulate the human
phenotype. Third, in both CNGB1-RP models rAAV gene augmentation therapy can efficiently (1) rescue the
function and (2) delay the degeneration of rods. There are four aims to the project: Aim 1 is development of an
optimized vector that efficiently and specifically targets rod photoreceptors in nonhuman primates. We will start
with an efficient vector with a new short rhodopsin promoter that has already shown efficacy in CNGB1-RP
animal models. The final rAAV-CNGB1 vector will be used to start the Good Manufacturing Practice (GMP)
process development. This final vector will be used to investigate duration of rescue achievable in mouse and
dog CNGB1-RP models and also answer the important question of "how late in the process of rod
degeneration can rescue and preservation of structure be obtained?” Aim 2 will consist of recruitment of
candidate patients for the clinical trial. A barrage of clinical testing methods will be used over a three year
period to precisely describe the RP phenotype and identify optimal outcome measures for a future clinical trial.
The testing will also ascertain if there is similar disease progression between the two eyes which would allow
the second eye to be used as a non treatment control. Aim 3 will consist of the animal toxicology and
pharmacokinetic and efficacy studies needed for IND submission. We propose a standard GLP
toxicology/biodistribution study in rats coupled with a hybrid efficacy/safety study using the CNGB1-RP dog
model. A pre-IND meeting with the FDA will review the study design and ensure that it meets regulatory
requirements. GMP vector production will then be completed. Finally, in Aim 4 we will prepare and submit an
IND application. This project fulfills the FOA goal of “development of a therapeutic, which can then be tested in
a clinical tria...

## Key facts

- **NIH application ID:** 9883002
- **Project number:** 5R24EY027285-03
- **Recipient organization:** MICHIGAN STATE UNIVERSITY
- **Principal Investigator:** WILLIAM W HAUSWIRTH
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,832,126
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9883002

## Citation

> US National Institutes of Health, RePORTER application 9883002, Translational Gene Therapy for CNGB1 Retinitis Pigmentosa (5R24EY027285-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9883002. Licensed CC0.

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