The transatlantic project
The PLN disease is a currently uncurable heart muscle disease caused by a genetic mutation in the DNA. Carriers of this mutation are exposed to a major health risk which may express itself in moderate to very serious heart failure, arrhythmias and sudden premature death. It concerns an “orphan”-disease for which more than about thousand carriers have been currently identified worldwide. It is almost certain that this gene mutation started around the 14th century in the North of The Netherlands and it was only been discovered in 2011 in The Netherlands. The PLN disease has revealed itself only rarely and can in those cases almost always be traced back to one Frisian ancestor. That’s why a large research project to find a treatment of this disease is very difficult to finance.
The PLN Foundation was founded in 2012 by people and family members affected themselves by the negative consequences of this 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 2 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.
PLN knowledge and experience
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 (AMC Amsterdam, 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. They will be working in parallel on 3 possible solutions:
1. Gene therapy: by inserting genetic material in human cells, one will try to replace the defective PLN protein by adding a healthy one. Prof. Dr. Hajjar (Cardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York City) has conducted a lot of PLN research projects and has ideas on how to get to a gene therapy.
2. 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 available in San Diego.
3. Stem cell therapy: inserting healthy stem cells in the heart muscle so that new and active heart muscle cells can be formed there.
Should possible therapies arise from these 3 solution paths, these will be validated by means of animal testing. Then, a “First-in-Man” therapy will be executed for the most promising solution. The latter obviously only once approval to do so has been obtained from the competent authorities.
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.
The total duration of the project is 5 years.
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 Dutch Heart Institute, an unique collaborative platform of the Cardiology departments of all 8 academic medical centers in The Netherlands. Within this institute, Prof. Dr. Doevendans will be responsible for the project supervision.
THE TOTAL COSTS OF THE PROJECT are estimated at 2.5 million euro. This means 500 thousand euro is needed annually during a period of 5 years. ALL contributions are extremely welcome!
Do you also want to help in offering some perspective to PLN gene carriers and family members and friends of carriers of this life-threatening disease?… thank you.
CALL for Project proposals
Are you maybe a trainee researcher and do you have some promising ideas of a succeeding output method for our PLN Project? Please apply and send us your Project proposal as next detailed. Thank you in advance for your contribution!