I am pleased to share an opinion article that I have written with Dr Dan Neill at Dundee University. We met through the UK NC3Rs (https://www.nc3rs.org.uk/) where I learnt about his an NC3Rs project within his lab. The project was to create upper airway mucus mimicking healthy and cystic fibrosis patients sputum which could then be used to study complex biofilm infections in CF patients.
The NC3Rs is very thoughtful about the 3Rs valley of death, i.e., a 3Rs advancement doesn't get used or further developed. After discussions with Dan, we thought there could be an interesting use of the sputum mimics in chronic and/or repeat dosing human in vitro toxicology testing and in further chronic efficacy testing human human in vitro models.
There are less concerns about this longer term approach from many colleagues creating and selling commercial human upper airway models or using the models in toxicology and efficacy testing. We know that the 3D upper airway models do have mucus reservoirs, although we do not know how long they last, especially over the chronic testing period of 28 or 90 days and especially with repeat dosing. However, we do want to progress the chronic testing using these and other complex in vitro models and to evaluate this issue ow should help us in getting as far with chronic in vitro respiratory toxicology testing as we have with acute respiratory toxicology testing.
We are looking for partners to join us in gaining funding to evaluate this in a spall proof of concept test. Please reach out to us especially if you have funding available or funding ideas for grant applications!
The formal reference citation is: Roper CS, Neill DR. Transitioning Acute In Vitro Inhalation Toxicology Testing to Chronic and Repeat Dose Testing; the Challenge of Mucus Depletion in Upper Airway Test Systems and Use of Sputum Mimics. Open Acc J of Toxicol. 2023; 5(4):555669. DOI: 10.19080/OAJT.2023.05.555669
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