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Five new grants awarded

Each year, the Dr Hadwen Trust funds pioneering medical research projects which benefit humans and animals. This year we are delighted to announce that we have been able to award even more grants than last year. Your help has made it possible to award five grants in diverse areas such as epilepsy, bone disease in childhood leukaemia, brain cell imaging and abdominal pain studies.

Epilepsy

Newcastle University, 2010 – 2012

Scientific studies of epilepsy currently use substantial numbers of laboratory animals worldwide, mainly mice and rats, and involve invasive brain studies. This project aims to replace models of epilepsy which use animal brain tissue with studies of live epileptic human brain tissue.

The research group has demonstrated that routinely obtained human epileptic brain tissue (from consenting donors) can be maintained in vitro to allow them to record a particular type of epileptic electrical signal not seen in animal studies. This approach offers accessibility and the ability to manipulate human epileptic brain tissue, which is not provided by animal or human clinical studies. The research group foresees that this will lead to a replacement of animal models of epilepsy both in vitro and in vivo.

Bone Disease

Cardiff University, 2010 – 2012

Bone pathologies (e.g. osteoporosis, osteonecrosis, arthritis-related bone loss, fractures) are major health problems. Despite several new treatments which have recently been launched, the challenge remains to develop further treatments and preventative regimes.

Currently, research into bone disease uses mice, rats, rabbits, pigs, dogs and sheep. These studies use large numbers of animals and often cause severe suffering, for example, rats being suspended by their tails for days to determine effects of taking the weight off their hind legs on bone quality. The new project aims to develop two different 3D cell culture model systems to maintain human bone cells as co-cultures

in vitro. These cell culture models will be used in the study of two areas of bone disease; the cause of osteonecrosis in childhood leukaemia; and signalling between bone cell types following mechanical loading (effects of friction, pressure, twist and weight on bones). An additional value of this project is that when established, these methods will be available for use by the wider bone research community.

Brain Cell Imaging

Birmingham University, 2010 – 2013

To cope with the ever-changing demands of the environment, the brain processes information about external events and internal thought processes, by means of its coordinated activity. The challenge is to develop techniques sensitive to millisecond by millisecond changes in this activity across all regions of the brain.

The biggest hurdle to the widespread use of brain imaging for the study of electrical brain activity in correlation with hemodynamic changes (changes in blood flow), is the identification of the best way to use and combine the data.

Two types of animal experiments are dominant in this field of research: invasive recording from non-human primates, usually rhesus monkeys; and invasive and in vitro recordings from adult mice, rats and ferrets. Both these techniques require surgical procedures to apply the electrodes to the animal brains and repeated anesthetisation of the animal, all of which carry substantial mortality risks. While non-human primate experiments are usually performed repeatedly on the same animal over its lifespan, these experiments in other animals are usually terminal, i.e. the animal is killed upon completion of the brain activity recordings.

This new project will develop the theory and practice of using non-invasive brain imaging techniques to show how the brain combines external stimuli with internal thought processes. The project will demonstrate the potential of this method of working with several brain imaging techniques to understand brain function.

Nanotoxicity Testing

Nottingham University, 2010 – 2012

Drug absorption using nanoparticles requires studying how nanoparticles can enter and distribute around the body. In vitro approaches to this work are required, as current animal models are not representative of human barriers. These animal studies use both normal and genetically altered mice, rats, rabbits, dogs and sheep with drug formulations administered through forced feeding or inhalation. The movement of nanoparticles into the body is highly dependent on the composition of the layers of cells and support structures found at the surface of the lungs and gut which are different in humans and animals.

This project will create several different cultures of human lung and gut surfaces to investigate the transport mechanisms of a variety of nanoparticles across these new realistic human cell surfaces.

Abdominal Pain Studies

Barts & Queen Mary’s, University of London, 2010 – 2013

Unexplained abdominal pain is a significant healthcare burden and one in which there is a current lack of effective treatments partly because of insufficient methods to directly study how this pain occurs in nerves. One step in developing new drugs for pain is the need to show that the drug is effective in reducing responses to painful stimuli and in particular in reducing the firing of pain transmitting nerves. Currently there are over 750 experimental animal studies reported which use mice, rats, guinea pigs, and cats. Many of these experiments and observations continue for prolonged periods in live animals.

The new project will use human tissue from the bowel (removed in the course of routine surgery) to study the firing of small sensory nerves in response to standard stimuli such as pressure and noxious chemicals. The project will develop a model, which is the first of its kind in any human tissue, by performing further detailed studies that could validate its use as a replacement for animal experiments. This can also be used as a platform for new drug testing.

The project demonstrates that advances can be made with human tissue using a translational multidisciplinary approach incorporating the expertise of clinicians (surgeons, pathologists) and non-clinical research staff.

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