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CRACKIT

CRACK IT Challenge 14: Inhalation Translation

About CRACK IT

The NC3Rs scheme under the CRACK IT Challenge 14: Inhalation Translation project outlines seven targets, which have been identified as major challenges facing the pharmaceutical industry in the development of inhaled medicines. 

The Challenge

  • Do foamy macrophages constitute an adaptive or adverse response?
  • Can we predict foamy macrophage development?
  • Achieving 3R targets in inhaled product development

Venn Diagram

Background

This project will develop novel technologies for assessing alveolar macrophage modulation and inflammatory responses during regulatory safety testing of new inhaled medicines. Outcomes will include important new insights into macrophage responses based on in vitro and enhanced, animal-sparing in vivo evaluations. ‘Foamy’ macrophage responses are commonly observed during non-clinical development, but are difficult to interpret. We have previously shown that the foamy macrophage presentation can be modelled in vitro, differentiated using a foamy macrophage toolkit which we developed in pilot studies, and characterised based on functional and phenotypic responses (temporal and dose-related) to different materials [Hoffman et al. In Vitro Multiparamater Assay Development Strategy toward Differentiating Macrophage Responses to Inhaled MedicinesMolec Pharm. 12 (8): 2675-87 (2015)]. Based on these high-throughput methods, we will develop predictive algorithms to prevent unsuitable compounds entering nonclinical testing. Biomarkers and further insights into macrophage responses will be sought using (i) state-of-the-art (and beyond) mass spectroscopy imaging of single cells and tissue slices, (ii) targeted transcriptomics / toxicological pathway analysis, (iii) parallel evaluation of non-invasive monitoring techniques for longitudinal studies: exhaled breath analysis. These approaches have been selectively combined by an expert multi-disciplinary consortium which, with the advice and in-kind contributions of industry sponsors, will deliver a high-value solution to the inhalation translation challenge. 

The Consortium

Who is involved?

The Consortium

Contact Us

Professor Ben Forbes
Telephone number: +44 (0)207 848 4823 
Email address: ben.forbes@kcl.ac.uk 

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