# Development of gene therapy product for treating MPS IIIB

> **NIH NIH R44** · NEUROGT, INC. · 2024 · $456,414

## Abstract

Project Summary
The goal of this fast-track SBIR project is to further develop AAV gene therapy product for treating
Mucopolysaccharidosis (MPS) IIIB towards clinical application and commercialization.
MPS IIIB, is a rare autosomal recessive lysosomal storage disease (LSD) caused by defects in α-N-
acetylglucosaminidase (NAGLU), a lysosomal enzyme essential for the degradation of heparan sulfates, a
class of biologically important glycosaminoglycans (GAGs). The lack of NAGLU activity results in lysosomal
GAG storage in cells in virtually all organs, leading to severe neurological manifestations, broad somatic
disorders and premature death. No treatment is available for MPS IIIB. Gene therapy (GT) targeting the root
cause has been considered to be an ideal strategy for treating monogenic diseases including LSDs. Numerous
studies have demonstrated the success of systemic trans-BBB-neurotropic AAV9 gene delivery for treating
neurogenetic diseases. Importantly, the efficacy and safety profiles of systemic rAAV9 gene delivery have
been demonstrated to be highly reproducible across different LSDs. To address the unmet need, we
developed new GT products for MPS IIIB, using the AAV9 vector platform to deliver a codon-optimized human
NAGLU cDNA (hNAGLUop). The codon-optimization resulted in enhanced expression and rNAGLU secretion,
indicating the potential for added by-stander effects. In preliminary studies, we tested these in MPS IIIB mice
and were able to identify the optimal vector product for further development. With an IV injection of the
designated optimal rAAV9-hNAGLUop vector in MPS IIIB mice, we achieved functional correction and reversal
of neurological and somatic disorders of MPS IIIB, strongly support the therapeutic potential of the proposed
rAAV9-hNAGLUop vector product for treating MPS IIIB in humans. We believe that we are well-positioned to
move forward towards a Phase I/II IND.
In order to efficiently develop the rAAV9-hNAGLUop GT product, this Fast-Track SBIR proposal will address the
critical challenge in developing AAV GT, the scale-up vector manufacturing. In Phase I studies, we will perform
the engineering trials of the scale-up rAAV9-hNAGLUop vector manufacturing (Aim #1) to develop and optimize
the procedures, based on the protocols and procedures currently used by Dr. Fu’s team. The vector products
will be tested in vitro and in vivo for qualification and SOPs will be developed. Once validated, in Phase II, we
will build a facility with two GMP manufacture suites using certified modular cleanrooms (Aim #2), in order to
produce rAAV9-hNAGLUop vector for our planned IND and eventual clinical application and commercialization.
In Phase II stage of this SBIR, we will also hold the Pre-IND meeting with the FDA for advice on our planned
Phase I/II GT clinical trial and then submit the IND package to the FDA for approval (Aim #3). The success of
this Fast-track SBIR project will enable the efficient development of the MPS IIIB GT pro...

## Key facts

- **NIH application ID:** 10921942
- **Project number:** 1R44NS135667-01A1
- **Recipient organization:** NEUROGT, INC.
- **Principal Investigator:** Douglas M McCarty
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $456,414
- **Award type:** 1
- **Project period:** 2024-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10921942

## Citation

> US National Institutes of Health, RePORTER application 10921942, Development of gene therapy product for treating MPS IIIB (1R44NS135667-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10921942. Licensed CC0.

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