Mitral Valve Research Update (Mitral Valve Endocardiosis - MVE).
This project is jointly funded by the Cavalier King Charles Club and the Kennel Club Charitable Trust. Part of the funding is being used to support Richard Han as a PhD student, and the remainder to cover the research consumable costs of the project. The project is now in its second year, and is attracting additional researchers to the group, helping us to answer different questions about this disease.

The initial intention of the project was to describe the changes in the cell profiles and morphology of the valves and see if this could give us any clues to the possible cause of MVE. This aspect of the project is going well with samples having been obtained from 24 affected dogs. The valve samples have been obtained from a variety of pure breed and mixed breed dogs, but so far we have very few valve samples from Cavalier King Charles spaniels. Furthermore, we are having problems obtaining tissue from normal dogs, but we hope in due course this will be resolved.

The morphology project will continue until sufficient numbers of valves have been evaluated for each grade of disease (there are 4 grades recognised). The data collected so far indicates that the cells in the affected valves transform into new cell types, and the questions are what triggers this transformation and does this result in the damage to the valve leaflets. In due course we will evaluate approaches that might allow us to answer these questions. Part of this aspect of the work is to be published in the American Journal of Veterinary Research shortly. Additionally, we had a Summer Vacation Studentship (Elaine Sheehan), funded by the Veterinary School, to look at changes in cell numbers in diseased valves. She found that there is no change in the numbers of cells in diseased areas of the valves, which contradicts what was previously thought to be the case. This data fits in another little piece of the jigsaw, and Elaine will present her data at the British Small Animal Veterinary Congress in Birmingham in April. She will continue her work with Richard during her final clinical year at college. An additional intercalated BSc student, Caroline Clark (a second year vet student) is also working with Richard looking at changes to the cells that line the valve surface. These cells (endothelial cells) are believed to have a potential role in the development of MVE.

With regard to Richard Han's plans, he had hoped to use a powerful molecular genetics approach to try and more quickly identify what is happening in diseased valves. This technique is called microarray, and allows the identification of what genes are switched on, and which are switched off, in any type of tissue. It is not a technique for identifying inheritance patterns. The technique is very expensive, and unfortunately a bid to the Petsavers Charitable Trust of the British Small Animal Veterinary Association for 5,000 was unsuccessful. However, we intend to apply to the American Kennel Club Canine Health Foundation shortly to see if we can secure this funding.

On a more positive note, we have recruited a new PhD student, Mojataba Hadian, who is a veterinary surgeon from the University of Urmia in Iran. He is funded by the Iranian government, and in addition to helping Richard with his project, he will be looking at the organisation of collagen in MVE. Collagen damage is one of the cardinal features of MVE, but we know very little about this damage. Mojataba will use a powerful x-ray technique, using facilities in Darnesbury near Warrington and in Trieste, Italy, to characterise the degree of loss of collagen, the type of collagen and the manner in which it is organised. A further addition to the team is Geoff Culshaw. Geoff has taken up the position of Lecturer in Cardiology at the veterinary school and will be looking at the nerve fibres that are in the valves of dogs with MVE. This is a completely novel area of research. We know nothing about what happens to the nerves in the diseased valve, but we do known such nerves have important control over cell function. This work will augment the rest of our studies.

Overall the project is proceeding well, with additional strands of research being explored and developed and more researchers wanting to get involved. It was always the intention of using the support from the CKCS Club and the Kennel Club Charitable Trust to provide the initial impetus to more expansive research into the basic science of this disease. That way we are more likely to solve the problem of MVE.

In the meantime we still need to collect tissue samples. We are having a positive response from veterinary colleagues in practice in the UK ad even from as far afield as Scandinavia. We would urge CKCS owners to be aware of our work and how they might help.
Dr B M Corcoran
Hospital for Small Animals
The University of Edinburgh
16th March 2005

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