# Targeted ColQ gene therapy for Congenital Myasthenic Syndromes

> **NIH NIH R42** · AMPLO BIOTECHNOLOGY, INC. · 2024 · $207,090

## Abstract

PROJECT SUMMARY
Congenital Myasthenic Syndromes (CMS) are a group of clinically similar neuromuscular transmission
disorders that differ in their underlying genetic mutation. While some phenotypical variation exists, CMS are
commonly characterized by muscle weakness (myasthenia) that worsens with physical exertion. Defects in
Collagen Q (ColQ), a multidomain functional protein of the Neuro Muscular Junction (NMJ) responsible for
AChEticholinesterase (AChE) anchoring and Muscle specific Kinase (MusK) phosphorylation, lead to
endplate AChE deficiency and ColQ CMS. ColQ CMS is a severe, pediatric orphan disease with a prevalence
of approximately 1,600 people in the major developed countries. Severe ColQ CMS can result in early death
and causes decreased Quality of Life due to extreme fatigability, dependency on intermittent respiratory
support, and/or tube feeding, which occurs in 2/3 of patients by early adulthood. No cure nor standardized
treatment has been yet developed for ColQ CMS. While some CMS subtypes are managed via administration
of AChE inhibitors, ColQ CMS is refractory and can deteriorate if treated with AChE inhibitors. Best available
care involves chronic administration of ?2-adrenergic receptor agonists, which only provide modest
symptomatic improvements. Amplo Biotechnology is developing treatments for CMS, seeking to streamline
the process of testing new adeno-associated virus (AAV) by applying a platform approach whereas, by using
the same gene delivery system and manufacturing methods, subsequent indications can be targeted by
changing the animal model and the transgene delivered. This approach will save time, money and will
ultimately allow to address the unmet needs of smaller patients’ populations where traditional drug
development investments cost are commercially unviable. AMP-201, is the first gene therapy product for
ColQ CMS, based on an AAV8 vector carrying the human ColQ gene. The development pathway presented
has been based on regulatory (pre-IND, pre-CTA) and scientific advice (TACT, Treat-NMD) provided for a
closely related gene therapy that Amplo is developing for Dok-7 CMS (Fast-track SBIR recently awarded).
Preliminary results in a ColQ CMS mouse model show that intra-venous injection of a AAV8-COLQ is able
to correct the pathological signs of AMP-201 in the ColQ -/- mice model which recapitulates the phenotype of
ColQ CMS. AMP-201 will enable a shift in the current clinical practice from chronic administration of drugs to
alleviate symptoms to a one-off treatment allowing physicians to treat the entire affected population, curing
adult disease, and stopping disease progression in children. The goal of this STTR Fast-Track project is to
validate the efficacy and safety of using AMP-201 for ColQ CMS. Amplo will use Phase I activities to perform
a pre-clinical dose-finding and efficacy study in ColQ -/- mice. The outcome of Phase I activities will be used
to direct toxicity studies in mice and pivotal DMPK/ADME and...

## Key facts

- **NIH application ID:** 10849629
- **Project number:** 5R42NS127713-02
- **Recipient organization:** AMPLO BIOTECHNOLOGY, INC.
- **Principal Investigator:** RICARDO Anibal MASELLI
- **Activity code:** R42 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $207,090
- **Award type:** 5
- **Project period:** 2023-06-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10849629

## Citation

> US National Institutes of Health, RePORTER application 10849629, Targeted ColQ gene therapy for Congenital Myasthenic Syndromes (5R42NS127713-02). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10849629. Licensed CC0.

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