Updated 2016 figures from the WHO have indicated that over 17 million people per year die from a cardiovascular disease (CVD), representing nearly one third of all deaths worldwide. The mortality is not exclusive to western cultures and economies with greater than 75% of those deaths occurring in low and middle-income countries.

 

More people die from a cardiovascular disease than any other cause, and in most cases the disease could be prevented by addressing lifestyle behaviours. In the United states alone over 2000 people die a day from CVD; that’s one person every 40 seconds.

 

The societal and personal costs for caring for and supporting patients with cardiovascular diseases are enormous: at a last analysis the direct and indirect costs of CVD totalled more than 320 billion dollars in the United States.

 

In the Western world presently there are over 9 million people suffering of heart failure where the treatment available (with the exception of heart transplant) are only palliative. Yearly, more than a million new patients join this group. The average life-span after the first episode of heart failure for these patients is of ~5 years.

 

The exception to behavioral change is the increased prevalence of degenerative diseases with the growing aged population, which has stimulated a growth in the need for effective and widely applicable therapies. Today there are 600 million people in the world aged 60 years or over, and this will double by 2025 and reach 2 billion by 2050. Degenerative diseases, in many cases not directly related to CVD present comorbidities that result in CVD occurring.

 

There is an urgent and critical need to target CVD at all levels: education to the young through to old on lifestyle changes, better diagnostics and care, more broadly acting therapies that specifically target the disease itself and associated pathologies.

Within MitoCardia this final point is our area of expertise, and during the next 5 years we will address this in significant detail to generate the following:

 

Novel insights based on high quality new knowledge

 

To achieve this we have brought together the global pioneers and opinion leaders in our area of research focus, who have made and continue to make seminal contributions in the area of cardiovascular research and mitochondrial role. They are established teams in their respective nations, with the plaudits and infrastructure to match and have collaborated for many years. With the support of Leducq funding and within a world first network that focuses exclusively on mitochondria in CVD, the partners are now enabled to answer pivotal and fundamental questions on why the mitochondria start to dysfunction, the molecular mechanics of this occurrence and its precise relevance in CVD.

 

Innovative therapeutic strategies that offer the potential for rapid solutions

 

The network will be drawing on previous work by the teams of the network that utilized the resources of the NIH Molecular Libraries Probe Production Centers Network to identify and optimize highly selective new therapeutic options. Several were identified from this study exhibiting high potency while importantly, simultaneously elicited no deleterious effects on the cells bio- energetic processes. We will be refining these promising compounds through state of the art chemical engineering to optimise their pharmacokinetics and pharmacodynamics to permit a better targeting and consequent smooth transition into clinical testing.

 

Understanding of Mitochondrial function/dysfunction and its relevance to other tissues and comorbidities

 

The outcomes of our work have a direct and clear impact on the global population suffering from cardiovascular disease; mitochondrial dysfunction is proving to be a pivotal component at the cellular level which results in inappropriate cell death, which when occurring at a high enough frequency results in significant localised cell death, which your body becomes unable to clear correctly setting in process a self perpetuating multifaceted vicious cycle occurring over a long period of time resulting in CVD events; the outcomes are death or a drastically reduced quality of life.

 

The process of mitochondrial cell death is however not exclusive to CVD, and occurs in many diseases and many organs; for example in many age related diseases such as muscle wasting (Sarcopenia), and rare muscle diseases such as Muscular Dystrophy, Mitochondrial dysfunction is heavily implicated. In both these diseases, cardiomyopathies are the main cause of death.

Therefore by targeting mitochondrial dysfunction, a developed therapeutic will be able to provide benefit for multiple simultaneous diseases; this reduces polypharmacy and healthcare costs.

 

Our insights based on new knowledge and potential therapeutic targets will therefore inform parallel fields of endeavour and provide opportunities to identify novel therapeutic approaches for other diseases that manifest similar mechanisms.

For more detailed and scientific information on mitochondria, mitochondria dysfunction and CVD please read: 

IMPACT

Relevance of Mitochondrial Dysfunction in disease. All the diseases indicated are known to have mitochondrial damage as part of the underlying pathology. Those indicated in blue are known to present as comorbidities with cardiac damage, (figure adapted from The Foundation for Mitochondrial Medicine)