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EU Training Network on Novel Targets and Methods in Atrial Fibrillation

Periodic Reporting for period 2 - AFib-TrainNet (EU Training Network on Novel Targets and Methods in Atrial Fibrillation)

Reporting period: 2017-09-01 to 2019-08-31

Atrial fibrillation (AF) is a complex and multifactorial disease. It is the most common cardiac electrical disturbance, occurring in 1-2% of the population. AF has rapidly become one of the most important public health problems in developed countries. This is due to its disproportionate effects on the elderly, who are growing in numbers thanks to the ageing population in regions like Europe and North America. More than 6 million Europeans suffer from this arrhythmia and its prevalence is expected to more than double in Europe during the next 40 years due to increased life expectancy. Hence, atrial fibrillation has assumed epidemic proportions.

AF is not only dangerous – associated with a twofold increase in mortality – it is also expensive, and places a huge burden on healthcare systems. The European Society of Cardiology estimates that at least 1% of the European healthcare budget is currently spent on AF management, equating around 13.5 billion EUR. Despite this, observers have concluded that available strategies for treating this condition are inadequate.

AFib-TrainNet is a European Training Network (ETN), which has been focusing on Novel Targets and Methods in Atrial Fibrillation. This network includes 15 PhD students and a number of European academic and industrial organisations. The involved researchers/biotech companies all provide a unique and highly effective platform enabling research collaboration around discovering and evaluating novel targets and methods for AF treatment.

The overall objectives of the AFib-TrainNet program has been to: i) Increase understanding of the underlying mechanisms of AF, ii) develop new research tools and methods to scrutinize AF, iii) evaluate two new pharmacological targets for AF treatment, and iv) train 15 ESRs in multidisciplinary research and outreach within the cardiac field.

We have obtained the following goals: i) Through a large number of scientific publications we have revealed a sum of new and highly interesting aspects of atrial fibrillation, ii) developed a number of new research tools spanning from atrial hiPSCs to horses as an AF model, iii) performed a number of successful studies with potential new anti-AF compounds, and iv) finalizing a very broad and high level training program for the 15 ESRs.
In the 2nd reporting period we have had profound focus on the following three activities:

i) training and education of the ESRs
A pivotal part of the network’s activities are focused on excellent training of the 15 PhD students. The training part in the network is meant in a broader perspective with focus on both scientific training, industry training and complementary skills. The students have participated in a number of AFib-TrainNet educational activities, including both focused and broad scientific learning and dissemination and more generic skill-set training. Also, industrial training has been a pivotal element as it has been our ambition to familiarize the ESRs with the work flow, scientific and mercantile focus, and work culture in the private sector. In addition to the AFib-TrainNet activities the ESRs have also participated in courses and training activities at their local universities. To ensure progression and competent and present supervision the biannual AFib-TrainNet meetings have all included sessions where the progression and satisfaction of the individual students were discussed.

ii) network activities
Apart from the many training events for the AFib-TrainNet students, the major common events have been the biannual meeting for both ESRs, supervisors and associated members of AFib-TrainNet. These meetings have had a multitude of focusses addressing both specific issues within the AF field, but also having presentations of broader scientific areas, as well as input from industry partners and invited speakers and generic skills presentations. A highly important output from these meetings have been the individual one-to-one meetings during the breaks. It has been in these meetings/discussions that highly interesting research questions have been discussed and where cross-country and interdisciplinary research projects have been initiated.

iii) research and scientific outreach
Outreach in AFib-TrainNet has been achieved on many levels, reaching from strict scientific journal publications to layman presentations to clinical development to transfer of know-how through secondments. All ESRs have produced high-level scientific publications (either already published or submitted). The students have participated in a multitude of outreach activities, functioned as teachers on courses for undergraduate students, and acquired many new technical skills and transferred these to colleagues. Another pivotal aspect of the AFib-TrainNet consortium is to provide the PhD students with a broad and international mind-set, which contributes to general outreach over the confined boundaries of the laboratory in the host institution. This is achieved by having an extensive network of exchanges of the students between the different countries and institutions.
With the AFib-TrainNet it has been our ambition to mature, define and develop new targets for treatment of atrial fibrillation. Simultaneously we have aimed at training and educating top-end young researchers.
An important part of the network's activities are centered on developing new tools to investigate atrial fibrillation, being applied for analyses of both the mechanisms leading to atrial fibrillation and of new treatment modalities. As a consequence we have developed three large animal models of atrial fibrillation, being goat, pig and horse, as well as scrutinized the usability of cardiac hiPSCs and combining all the data in in silico models. Another pivotal part of the scientific activities has been to test whether pharmacological targeting of two different atrial ion channels (SK and GIRK channels) can be anti-arrhythmic. By applying the applying the developed models with the pharmacological testing we have in a multitude of experiments found that SK channel inhibition is a very promising target and that GIRK channels as target for AF treatment may be potential modality on certain circumstances.
Hence, overall we have delivered ground-breaking results which will be highly valuable for companies and clinicians developing novel treatments of AF. A very direct effect of our research activities is that Acesion Pharma, which is one of the beneficiary companies, have started clinical phase 1 and phase 2 trials of SK channel blockers in humans.

The other goal of our network was to train and educate 15 ESRs. We have delivered a training program which has been very intense, providing the students with both specific cardiac knowledge and more general and generic skills know-how. This has been performed with a cross-sectoral focus, including both clinical work and company awareness. In addition to this academic training the ESRs have been acquainted with a numerous methodologies and been expert in several. At present several of the ESRs have passed their final PhD examination and the remaining are working on writing their thesis. Hence, with the training program in AFib-TrainNet we have produced 15 highly skilled young researchers which are ready to start a career in both industry and academia. And they will for sure produce an impact in the future for the benefit of the European medical industry and finally the many AF patients.
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