Transatlantic collaborative project, 2017 – 2022
The PLN Foundation was founded in 2012 by people and family members affected themselves by the negative consequences of the PLN gene mutation. During the first years, scientific research projects were mainly 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. They jointly 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 treatment method.
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 method 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. Initial they were be working in parallel on 3 possible solutions:
Gene therapy: by inserting genetic material in human cells, one will try to replace the defective PLN protein by adding a healthy one.
Drug therapy: investigating whether existing drugs or specific molecules have a favorable impact on the PLN mutation. The advantage 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 availablein the USA.
Stem cell therapy: inserting healthy stem cells in the heart muscle so that new and active heart muscle cells can be formed there. Stem cell 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 gene expression in a cell to prevent the expression of a certain gene.
An 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 animal proofs and after that the “First in Man” therapy will be tested. Of course after all approvement from the involved organizations and regulations.
An important argument for this project, is the spin-off which largely consists of a deeper understanding of the heart muscle cell operation and particularly the functioning of the calcium balance which makes the heart muscle contract and relax. This may possibly also be applied when finding treatment methods for heart failure, one of the main causes of death worldwide.
The management of the research project is conducted by the Netherlands Heart Institute, an 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 project supervision.
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 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.