# Rifampin potentiation in NTM

> **NIH NIH R41** · SPINCEUTICA, INC. · 2020 · $205,299

## Abstract

Non-tuberculous mycobacterial lung disease (NTM-LD) caused by Mycobacterium avium complex is a serious
chronic infection causing permanent lung damage, and is difficult to treat, typically requiring 12-24 months of
treatment with rifampin, macrolide and ethambutol.
We hypothesize that combined deuterated ambroxol and [acyl-13C]INH will allow both pharmacokinetic
and pharmacodynamic enhancement of Rif activity against MAC to dramatically improve therapy. To
test this hypothesis we propose these aims.
Specific Aim 1. Determine the resistance of deuterated ambroxol and controls to Cyp3A4 metabolism
using Supersomes. We will use industry standard Corning® Cyp3A4 Supersomes™ to determine resistance of
ambroxol-d2 to in vitro metabolism using HPLC, MS and 13C-NMR assays.
Specific Aim 2. Quantify rifampin, [acyl-13C]INH and ambroxol-d2 efficacy by combination treatment
activity against a clinical isolate of Mycobacterium avium in a chronic mouse aerosol infection model.
The model will also evaluate the ability of a combination treatment to penetrate the established granuloma and
access the internalized bacilli.
At the end of this Phase 1 STTR project we will have determined whether deuteration can solve the Cyp3A4
metabolic liability of Amb, and whether ambroxol-d2 and [acyl-13C]INH, separately and combined can potentiate
MAC treatment in in a highly predictive mouse model, setting the stage for Phase 2 proposal.

## Key facts

- **NIH application ID:** 9908969
- **Project number:** 1R41AI145461-01A1
- **Recipient organization:** SPINCEUTICA, INC.
- **Principal Investigator:** GRAHAM S TIMMINS
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $205,299
- **Award type:** 1
- **Project period:** 2020-02-19 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9908969

## Citation

> US National Institutes of Health, RePORTER application 9908969, Rifampin potentiation in NTM (1R41AI145461-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9908969. Licensed CC0.

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