Project: Development of innovative diagnostic and prognostic tools for the canine and human mitral valve disease.

Aim of the program_x000D_The aim of the 3 years project CARDIOMARKS is to develop cost-effective diagnostic and prognostic markers for veterinary screening for a cardiac disease: the degenerative mitral valve disease (DMVD). In addition, these markers will be evaluated for prognostic use of the homologous disease in humans. These markers are genetic markers, allowing development of DNA tests and circulating proteins allowing the development of ELISA tests. It is expected that a better understanding of a dog model used in this project, in particular its pathophysiology, will provide the basis for new therapeutic approaches (not pursued in the project)._x000D__x000D_State of the art_x000D_This project, named CARDIOMARKS, is motivated by_x000D_1- The recent effort made for comparative model_x000D_The European Community supports the LUPA project (2008-2011), which aims at unravelling the molecular basis of common complex human disorders using the dog as a model system. Some studies have already proved the value of this model for the humans (1,2) and some promising results require further investigations for cardiac diseases. _x000D_The canine model has distinctive advantage over existing rodent models and we propose to use spontaneous canine DMVD as a powerful comparative model for human homologous diseases, named “mitral valve disease” in this project. Considering the genetic heterogeneity and the variation of the aetiology in human, we believe that purebred dogs, as quite homogenous genetic isolates, can significantly help to better understand and diagnose these severe cardiac ailments and to advance medical genetics._x000D_2- The high incidence of the mitral valve disease in humans and dogs_x000D_Although not as common as coronary cardiac disease, heart failure or hypertension, valvular heart disease is an important and challenging clinical entity. Particularly, mitral valve disease leads to affect the structure and function of the mitral valve and then to the progressive myocardial dysfunction and cardiac failure. The mitral valve disease constitutes a heterogeneous disease and very little is known about the genetic background. Some similarities exist between the evolution of this disease in humans and dogs: the thickening of the valve leads to mitral regurgitation and, possibly, to cardiac insufficiency. In both cases, the disease can evolve silently until a sudden complication._x000D_The most frequent congenital valve defect affects about 1% of the general human population._x000D_The genetic valvular disease observed in dog (DMVD) is present in the general canine population and is highly prevalent in some dog breeds in which DMVD was unintentionally selected and disseminated. For example, 9% of Yorkshire Terrier (YT) are affected at 6 year-old. Other breeds are also affected: Cavalier King Charles, Dachshund, Poodle, Shih-Tzu, Lhassa-Apso, Bichon (3,4)._x000D_3- The management of the patient is better if the disease is early detected. _x000D_Whether for humans or dogs, we must await the clinical signs. Currently, no prospective pharmalogical clinical trial has demonstrated any capability to affect the natural course of spontaneous native valve degeneration. The treatment requires chirurgical operation, for which the risk is related to patient age, among other things._x000D_4- Specific markers do not exist_x000D_The current markers are related to the general heart health. That is, plasma N-terminal pro-B-type natriuretic peptide concentration helps to predict survival in dogs with symptomatic degenerative mitral valve disease as it is a marker of general cardiac dysfunction_x000D__x000D_Objectives_x000D_The tests we aim to develop will allow detecting patients at risk and offer them a dedicated follow up to result in improved lifespan and fewer complications. Such tools do not exist today. The evolution of the disease varies with the patient, hence detailed diagnosis and prognosis will be required, and the project is set up to provide such endpoints. Last, the markers could provide leads for therapy._x000D_By using two complementary approaches, DNA and protein, the consortium strengthens his chances of identifying relevant markers. _x000D__x000D_The multidisciplinary skills of the Ps (See figure 1 in annexe), including two SMEs allow achieving the overriding objective of CARDIOMARKS: to identify and compare genetic and protein biomarkers available in one species, and test their utility in both humans and dogs. These complementary skills gathered in the consortium are: the clinical cardiac evaluation of the dogs (INSERM-UCA), the canine (ANTAG) and human (INSERM-IT) genetics, the expertise in protein fields (BDF), the validation with mouse model (U-STRASBG) and development and commercial side for expected products (ANTAG, BDF)._x000D__x000D_Our effort shall provide reliable markers enabling to develop genetic and biological tests. The consortium will focus on the dog but will be able to translate its findings to humans because of the skills and expertise available in the scientific teams working on the homologous disease in humans.

Acronym CARDIOMARKS (Reference Number: 6490)
Duration 01/01/2012 - 31/03/2015
Project Topic The aim of CARDIOMARKS is to develop cost-effective diagnostic and prognostic markers for the degenerative mitral valve disease, allowing DNA tests for canine breeds and ELISA tests for dogs and humans. The innovative approach will compare both species dog and human with genetic and protein studies.
Project Results
(after finalisation)
The aim of the CARDIOMARKS project in our organization was to develop cost-effective diagnostic and prognostic markers for the degenerative mitral valve disease, allowing ELISA tests for dogs and humans. Two ELISAs which have been developed in the course of the project as related to cardiac disease have been adapted for human samples and are being marketed (endothelin, sRANKL), a HPLN1 ELISA is in final development. Another ELISA, for NT-proCNP, has been adapted into a lateral flow assay format for dog samples. The assay has been licensed to a US company specialized in veterinary diagnostics for the US market.
Network Eurostars
Call Eurostars Cut-Off 6

Project partner

Number Name Role Country
6 ANTAGENE Coordinator France
6 Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire Partner France
6 Laboratoire de Neurobiologie et Pharmacologie Cardiovasculaire Partner France
6 INSERM UMR915 Partner France
6 The Antibody Lab GmbH Partner Austria
6 INSERM-U955 Partner France