To develop and launch of a new-to-market 'QV CardioBox, which provides an off-the-shelf solution for in-vitro tests for the monitoring of safety and/or efficacy of compounds in the cardiovascular system.

The blood–brain barrier (BBB) is composed of different specialised cell types and regulates exchange of substances between the blood and the brain. There are a large number of diseases including stroke, brain trauma and tumours in which the permeability of the BBB is increased. Conversely, many drugs are unable to cross the BBB to reach the brain making the BBB one of the major obstacles in the treatment of the brain diseases. Proper regulation and maintenance of BBB is, therefore, essential for effective drug delivery to the brain to cure brain diseases and preventing its further damage. In this project we aim to develop a three dimensional in vitro BBB model using the Kirkstall Quasi-Vivo system which allows multiple cell types to be cultured in inter-connected culture chambers and a method of assaying the passage of of potential drugs across the BBB by electrochemical and laser biosensors. This in vitro model will be an important tool for investigation of different aspects of BBB function and testing potential drugs for their permeability and toxicity and reducing animal usage in this area. Human cell based models should be more accurate and predictive than animals.

Cardiovascular diseases account for more than 150,000 annual deaths in UK, affect more than 5 million people and cost more than £30bn a year to treat. To tackle this problem, drug companies and academics are trying to find new ways to expand our understanding of the causes of cardiovascular disease, and develop new ways of treating them. Usually, this research involves the use of animal models. Tests in animals are often unable to accurately predict what will happen in a human when a drug is given, leading to unexpected harmful effects in patients. The aim of our project is to develop a model of the cardiovascular system, using human cells, in a circulating system to allow the cells to communicate and detecting their response to drugs using state-of-the-art biosensor chips. This physiologically-relevant model will be a major step towards study of cardiovascular diseases and therapies in the laboratory without using animals. The models developed in this project could help drug companies identify which drugs are going to be useful and which drugs will be harmful, helping them to develop safe and effective new treatments for cardiovascular diseases, and saving human and animal lives.

Awaiting Public Summary

Kirkstall is developing in-vitro cell culture systems. It recently completed a GRD Research project which established the technical and commercial feasibility of using technology licensed from the University of Pisa, to detect chemical toxicity. The GRD project also enabled the company to transfer the technology from Pisa into its laboratories in Sheffield, and to incorporate it into its first product, the Quasi-Vivo™ cell culture kit. This GRD Development project will aim to demonstrate the functionality of Kirkstall's existing Quasi-vivo™ system in new applications and add new features to the product to create a second generation prototype. Both these developments will help Kirkstall to better match the needs and demands from an emerging market for animal-free testing of product safety and efficacy. Although the Quasi-Vivo™ system is already being used by the academic research community and for contract research, the product needs further development to meet the needs of the chemical, cosmetics and pharmaceuticals industry. Potential customers are looking for further evidence that the Quasi-Vivo™ system is more effective than existing methods. This project will aim to produce such evidence by investigating the correlation between existing in-vivo clinical data on 12 pharmaceutical and chemical com~ounds and the results from testing the toxicity of these same compounds in the Quasi-VivoT system. In addition it will add new features to the cell culture chambers to facilitate the optical observation of large cell colonies with 30 structure. This will be an important tool to aid the development of more representative tissue models for the study of chemical safety and toxicity.