Myxomatous Mitral Valve Disease Research
Royal (Dick) School of Veterinary Studies, The University of Edinburgh
Professor Brendan Corcoran

Heart Ultrasounds
A range of studies on myxomatous mitral valve disease (MMVD) are ongoing at Edinburgh some of which have been supported by the CKCS Club. The work is also supported by owners and breeders who have kindly allowed us to collect heart valves from their dogs, and without this commitment our work would be extremely difficult to carry out.

So how far have we got? Like most science research you often find you end up with more questions than answers, but the hope is you can identify the important questions that will eventually give you the right answers. In the case of mitral valve disease we want to know why it happens, how it happens and most importantly can we slow, stop or reverse the changes seen? The ultimate aim is prevention and failing that, cure.

Valve pathology:
We now know, from our own studies that the changes in the valves of CKCSs are similar to that seen in all dogs affected with the disease. This is important as it means information gleaned from any dog with the disease can be applied to the CKCS breed with a high degree of confidence. The further implication would be that any genetic cause of CKCSs likely affects the age of onset of the disease and not the eventual pathology.

We also know, and this was only pointed out to us by breeders and owners, that there are readily identifiable groups of CKCSs who do not get MMVD and another group who do later in life and remain unaffected. This suggests that MMVD in CKCSs is heterogeneous (has different forms) in the way it develops and provides a powerful model to allow us to identify the genes that drive this disease. At present we are examining, heart scanning, and collecting DNA from a large number of CKCSs across the UK. Again, we are extremely grateful to the many owners and breeders who have been so helpful with this project. The collecting work is being carried out by Dr Anne French (now at Glasgow Vet School) and Dr Simon Swift (now at University of Florida), and the DNA samples are stored at the Roslin Institute in Edinburgh. Funds will be needed at some stage to analyse all these samples, and we are liaising with colleagues world-wide to access similar stored samples, which will also improve chances of gaining funding. The material and information we have collected probably gives us the best opportunity to identify what if any is the genetic basis for MMVD in the CKCS.

We have generated a lot of useful data on the genes that are switched on and switched off in the severely affected CKCS valves. This gives us some insight into the possible mechanisms that might be driving the disease, but the problem is determining what is "cause" and what "effect" is. On the back of this study, which was part funded by the CKCS club, we have submitted further grant applications to try and answer that questions. We are interested to know how the expression of these genes might change as dogs get older and as the disease becomes more severe. We have also managed to identify from this study small pieces of genetic material which might be potential new drug targets. This is part of an exciting new scientific area called epigenetics, whereby genes themselves are controlled by other factors, including other genes. If we can manipulate these factors, and there is evidence from other diseases that this is possible, then we might be able to slow progression or even reverse the changes seen. A grant application has been submitted to try and get funds to answer this question.

Tissue Engineering:
Lastly, we are looking at a new approach to help us examine this disease more closely. Owners and breeders have been very supportive in helping us collect valves for our work, for which we are very grateful. But there is a limit to a how many valves we can collect and for a lot of owners the sadness of losing their pet just makes it too hard to agree to donate valves for research. So what if we could grow our own valves in the laboratory? That is what we are trying to do and we have funding to complete work started by one of our PhD students with the aim to have a working prototype within 12 months. If successful we can ask any biological questions we want and have a limitless supply of artificial valves to help us.

There are several other small pilot projects on-going and planned which hopefully will inform the next steps and get us closer to our goal. We constantly are look for funding from a range of sources and always acknowledge the important support of the CKCS Club. However, funding options are very competitive and there are a lot of other important canine diseases that we have to compete against for funds. So success is not always guaranteed, but fingers crossed we will get the funding we need.
Professor Brendan Corcoran Nov 2014
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