# Development and Validation of Therapy for Mucopolysaccharidosis III

> **NIH NIH U44** · PHOENIX NEST, INC. · 2022 · $2,435,870

## Abstract

Project Summary
Sanfilippo disease (mucopolysaccharidosis type III; MPS III) is a devastating neurodegenerative lysosomal
storage disorder of childhood whose pathologic features are neurologic: slowing of development, severe
behavioral problems, progressive cognitive decline, dementia, and decline in motor skills leading to immobility,
unresponsiveness, and death. We have focused on MPS IIID caused by a deficiency of alpha-N-
acetylglucosamine-6-sulfatase (GNS). Because MPS IIID is rare (1 in a million) and affects the brain (which is
difficult to treat) no cure or treatment is available and there are at least three patients in the USA to our
knowledge. Dr. Patricia Dickson and Dr. Tsui-Fen Chou (LABioMed) have developed an enzyme replacement
treatment (ERT) for MPS IIID. Our strategy proposes to deliver recombinant human alpha-N-acetylglucosamine-
6-sulfatase (rhGNS) intrathecally or intraventricularly to effectively treat the underlying causes of the neurologic
symptoms that dominate MPS III pathology. ERTs are not a cure but can have a dramatic effect on the quality
of life and patient development. There are several examples of successfully commercialized ERT's (e.g.
laronidase (MPS I), idursulfase (MPS II), etc) and Biomarin recently received approval for an ERT for a form of
Batten disease, CLN2. Other ERTs for MPS I, II, and IIIB are in Phase I trials. Both the FDA and investors are
familiar with ERT and its commercialization path, which will greatly increase the chances of reaching a clinical
trial. We have produced rhGNS ~200 µg per 750 mL media in CHO cells, purified it to a specific activity of
~100,000 activity units/mg, demonstrated maximal enzymatic activity at pH 5.6, which is closer to lysosomal pH
(with low activity at neutral pH), demonstrated good enzymatic activity at 37ºC and showed it is stable for over
one month at 4 ˚C in artificial cerebrospinal fluid storage buffer. We demonstrated intracellular uptake of rhGNS
in MPS IIID fibroblasts when rhGNS is added to the media and confirmed that radiolabelled HS diminished 33-
65% in MPS IIID fibroblasts treated with rhGNS (to wild-type levels). We have since scaled up our production of
rhGNS so that we can study enzyme activity, lysosomal storage reduction, neuropathology and half-life
estimation in the recently characterized MPS IIID knock out mouse. After dosing knockout mice with a single
dose of ~5.3 ug rhGNS we have observed return of GNS activity to 50% wild-type levels in mouse brain
and a statistically significant reduction of markers of lysosomal storage in this model (NAGLU and
hexosaminidase acitivity) after 1 day of treatment. Our currently ongoing studies include histology and half-
life estimates after repeat dosing in knock out MPS IIID mice. LABioMed has filed a US patent on rhGNS
(pending) and Phoenix Nest, Inc. has licensed it. The pre-IND studies we now propose through this program
would include transferring production to a GMP facility, optimizing process for s...

## Key facts

- **NIH application ID:** 9999403
- **Project number:** 5U44NS089061-05
- **Recipient organization:** PHOENIX NEST, INC.
- **Principal Investigator:** Tsui-Fen Chou
- **Activity code:** U44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,435,870
- **Award type:** 5
- **Project period:** 2014-09-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9999403

## Citation

> US National Institutes of Health, RePORTER application 9999403, Development and Validation of Therapy for Mucopolysaccharidosis III (5U44NS089061-05). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9999403. Licensed CC0.

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