Transatlantic collaborative project, 2017 – 2022
The PLN Foundation was founded in 2012 by patients and familymembers affected themselves by the negative consequences of the PLN-genemutation. During the first years, scientific research projects were initiated and financially supported in the Netherlands in order to gain more insight in this disease. During the last years, a global study was done to trace where knowledge and experience was available in the field of the PLN-mutation in order to develop a treatment for this life-threatening disease.
The conclusion is that there is knowledge about the PLN mutation in the Netherlands and that several studies are currently ongoing at the academic centers in Groningen, Utrecht and Amsterdam. These three together treat almost all Dutch PLN-patients.
In the United States of America, a number of technological innovations took place which can be used to conduct further research projects on finding a method for treatment.
Based upon the above, the PLN Genetic Heart Disease Foundation came up with the plan to establish a transatlantic collaborative project in order to try and find a treatment for this life-threatening disease.
The project involves the establishment of a unique collaboration between 3 academic medical centers in the Netherlands (Amsterdam UMC, UMC Groningen and UMC Utrecht) and 3 academic medical centers in the United States of America (Mount Sinai Hospital New York, Stanford University, California and the University of Cincinnati College of Medicine). This way, the best of the best in the field of knowledge and experience with the PLN mutation and the most technologically innovative institutes are brought together. Initially they will be working in parallel on 3 possible solutions:
Gene therapy: trying to replace the defective PLN-protein by adding a healthy one, through means of inserting genetic material.
Drug therapy: investigating whether existing drugs or specific molecules have a favorable impact on the PLN-mutation. The benefit of this therapy is that the valuable time of development, testing and having a new drug approved could be saved. For this purpose, an ultramodern robotized laboratory is available in the USA.
Stemcell therapy: inserting healthy stemcells in the heartmuscle so that new and active heartmuscle cells can be formed there. This therapy did not give the wanted results and therefor it was decided to focus on the other two therapies and gene-silencing. Gene-silencing is is the regulation of expression of a gene in a cell to prevent the negative expression of that certain gene.
The most important part of the research project will take place in America and will be supported by sending talented young medical scientists from the Netherlands who also will be financially supported. The other part will take place in the Netherlands.
When a solution is found in these therapies, it will be tested through tests on animals and after that the “First in Man”-therapy will be tested. Of course after all involved organizations have approved and regulations are established.
An important argument for this project, is the spin-off which largely consists of a deeper understanding of the workings of the heartmuscle cell and particularly the functioning of the balance of calcium which makes the heartmuscle contract and relax. This may possibly also be applied when finding treatment methods for heartfailure, one of the main causes of death worldwide.
The management of the research project is conducted by the Netherlands Heart Institute, a unique collaborative platform of the Cardiology departments of all academic medical centers in the Netherlands. Within this institute, Prof. Dr. Doevendans is responsible for the overall supervision of this project.
CURE-PlaN, 2019 – 2024
Mid 2018, Fondation Leducq awarded USD 6 million for a PLN-focused international research plan, the CURE-PLaN. This project officially started on January 1st, 2019. The team is a transatlantic team brought together by our Foundation, consisting of researchers from UMC Groningen, Amsterdam UMC, UMC Utrecht, New York Mount Sinai Hospital, University of Cincinnati and Stanford University (Mercola Lab). This team was further strengthened with researchers from Greece and Germany.
A first start was already made in the last quarter of 2018: the Netherlands Heart Institute and our Foundation took the initiative to organize a researchers day. Almost fifty researchers from the Netherlands, America, Germany, Italy and other countries took part. Timelines were discussed and agreements were made.
This project has led to some duplication with our existing project. In recent months the Netherlands Heart Institute has been working with us to remove these duplications from the project and to coordinate the two initiatives. Our goal is to support efficient initiatives that strengthen and accelerate the overall project.