NPL helping to CRACK IT
The National Physical Laboratory (NPL) has been awarded funding by the UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs), for a project which could help reduce the number of animals used for testing medicines to treat diseases like asthma.
The project funding was awarded as part of the NC3Rs' CRACK IT Challenges programme. This aims to solve five of the biggest drug discovery and development challenges facing the pharmaceutical industry, where the replacement, reduction and refinement of animals in research is the ultimate goal.
The 'Inhalation Translation' challenge, which NPL will be working towards solving, concerns chronic inflammatory diseases of the airways such as asthma and chronic obstructive pulmonary disease. Few new drugs have made it to the clinic during the past 50 years, with many that perform well in preclinical animal studies failing in humans due to lack of safety and/or efficacy.
The project aims to enable the non-invasive assessment of inflammation associated with drug toxicity in individual animals, rather than using multiple animals. This could reduce the numbers of animals used at certain stages of drug discovery and development. It would also make the data obtained from the assessment more reliable and less variable, potentially leading to earlier go/no-go decisions on a drug candidate that may otherwise fail later in development.
A specific and significant challenge is in understanding the response to drug treatment of macrophages - specialised cells that play a vital role in the immune system but can also cause inflammation. This requires measurements of the location of the drug inside the macrophages and the chemical changes that occur to the cells due to the presence of the drug.
NPL will develop these measurements using mass spectrometry imaging techniques, including Matrix-Assisted Laser Desorption/Ionization (MALDI) and Secondary Ion Mass Spectrometry (SIMS) . These can probe the distribution of drugs in macrophages, as well as the distribution of certain lipids, which act as biomarkers, signalling any adverse reaction. The proposed techniques will allow scientists to monitor multiple drug compounds, their associated metabolites and the lipid biomarkers, in a single experiment, reducing the need for multiple tests.
Dr Vicky Robinson, Chief Executive at the NC3Rs, said:
"In many cases drug-induced toxicity results in a significant number of new drugs failing before they reach the market place; often this is not identified until animal studies have taken place. By developing more predictive technologies and approaches for use in the earliest stages of drug development, industry scientists will be better equipped to identify whether a new drug is suitable for later-stage testing in animal studies and humans. This is not only more cost-effective, but has the potential to significantly reduce the number of animals needed overall."
The work at NPL will be carried out in the National Centre of Excellence in Mass Spectrometry Imaging (NiCE-MSI), which was established in partnership with the University of Nottingham to boost the application and impact of mass spectrometry imaging techniques, and led by Josephine Bunch.
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