# Title: Intracerebroventricular sulfamidase delivery to the Brain

> **NIH NIH R43** · TEGA THERAPEUTICS, INC. · 2020 · $258,169

## Abstract

PROJECT SUMMARY
MPS IIIA is lysosomal storage disease; a disease in which a key enzyme, sulfamidase (SGSH) is missing in
cells, resulting in the toxic accumulation of complex sugars called glycosaminoglycans, principally in the central
nervous system (CNS). A primary approach for treating related types of disorders involves replacement of the
missing enzyme by injection into the circulation. Enzyme replacement therapy resolves many aspects of the
disease but unfortunately it does not resolve complications of the disease in the CNS. This proposal focuses
on the development of a novel way to perform enzyme replacement therapy and its application to MPS IIIA, a
disease with severe neurodegenerative symptoms but with very limited current therapies due to poor transport
across the blood-brain barrier. We have tested our approach on a similar disease, MPSI; which is missing a
different key enzyme called iduronidase (IDUA). Using iduronidase (IDUA) conjugated to guanidinoneomycin
(GNeo), a molecular transporter, we showed that we can deliver the missing enzyme to cells derived from MPS
I patients and that intranasal administration of small amounts of the conjugated enzyme were sufficient to
reduce pathological glycosaminoglycans in the brain. The purpose of this grant is conjugate SGSH with GNeo
(GNeo-SGSH) and assess the effectiveness of enzyme replacement therapy delivered directly to the central
nervous system in the MPS IIIA mouse model using intracerebroventricular administration. Dose-dependent
biodistribution of GNeo-SGSH and effects on biochemical and histological pathology will be evaluated. Efficacy
and safety will be assessed in single dose and 2-week dosing studies. The results will provide the preclinical
information needed to proceed towards a novel treatment of the disease in humans.

## Key facts

- **NIH application ID:** 10010624
- **Project number:** 1R43NS115099-01A1
- **Recipient organization:** TEGA THERAPEUTICS, INC.
- **Principal Investigator:** Jillian R Brown
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $258,169
- **Award type:** 1
- **Project period:** 2020-04-15 → 2021-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10010624

## Citation

> US National Institutes of Health, RePORTER application 10010624, Title: Intracerebroventricular sulfamidase delivery to the Brain (1R43NS115099-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10010624. Licensed CC0.

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