Periodic Reporting for period 4 - CY-BIOBANK (Biobanking and the Cyprus Human Genome Project)
Période du rapport: 2023-10-01 au 2025-03-31
The problem relates to the lack of adequate research infrastructures in Cyprus, especially regarding medical genetics and genomics; hence it is a country of low performance in research and innovation. We are interested in a Biobank, as a medical research infrastructure that is a sine qua non instrument for motivating and fostering innovative translational research. Our group has started the first Biobank in the country in 2011 with external competitive funding, however, it was not adequate to satisfy the global need of the research community on the island, and most importantly it could not do justice to the many unmet clinical needs. With this new generous funding from the HORIZON 2020/TEAMING program, we aimed to upgrade the existing infrastructure into a Center of Excellence in Biobanking and Biomedical Research, in compliance with European standards and norms.
This new Center is destined to enhance the enrolment of large numbers of volunteers, healthy and affected with various genetic diseases, monogenic and complex, and generating Big Data of high quality, genetics/genomics, and else. This development is going to result in new opportunities and tools for improving the diagnosis, prognosis, and treatment of diseases, amongst many other objectives to the benefit of every citizen and society at large.
It is extremely important for society because having access to a contemporary Biobank the medical and research community will be able to develop innovative projects aimed to better diagnosis, prognosis, and treatment of medical conditions including the rare monogenic diseases as well as other more frequent multifactorial conditions, including diabetes, cardiovascular conditions, cancer, to name a few. New developments and discoveries to emanate from research in the next few years will result in improving the quality of life of patients as well as lead to the evidence-based establishment of new public health care policies, to be implemented by the Ministry of Health. Therefore, this project in addition to its scientific goals, it addresses unmet societal needs in a global manner, promising to save lives and reduce the health care budget in the long run.
This new Center is destined to enhance the enrolment of large numbers of volunteers, healthy and affected with various genetic diseases, monogenic and complex, and generating Big Data of high quality, genetics/genomics, and else. This development is going to result in new opportunities and tools for improving the diagnosis, prognosis, and treatment of diseases, amongst many other objectives to the benefit of every citizen and society at large.
It is extremely important for society because having access to a contemporary Biobank the medical and research community will be able to develop innovative projects aimed to better diagnosis, prognosis, and treatment of medical conditions including the rare monogenic diseases as well as other more frequent multifactorial conditions, including diabetes, cardiovascular conditions, cancer, to name a few. New developments and discoveries to emanate from research in the next few years will result in improving the quality of life of patients as well as lead to the evidence-based establishment of new public health care policies, to be implemented by the Ministry of Health. Therefore, this project in addition to its scientific goals, it addresses unmet societal needs in a global manner, promising to save lives and reduce the health care budget in the long run.
Between October 2023 and March 2025 (M9-M66), the CY-Biobank project achieved significant milestones.
Notably, it delivered 1446 whole exomes of Cypriot volunteers through collaboration with the Regeneron Genetics Center and a private biotech, with plans for additional sample sequencing aiming for a total of 5000. This reflects for the first time a good representation of the Cypriot reference genome, with many potential applications in health and disease.
In the domain of genetic modifiers impacting kidney function, the project is preparing a major manuscript on severe kidney function decline in patients with mutations in COL4A3 and COL4A4 genes. Progress includes a preclinical study on Alport syndrome and detailing more than 300 Cypriot families with suspected inherited heart and kidney conditions, which were referred for genetic investigation.
A groundbreaking clinical trial on MUC1 kidney disease was initiated in two Cypriot cohorts in collaboration with the Broad Institute of MIT and Harvard. Also, the Biobank expanded to nearly 11000 volunteers, plus several hundred follow-up samples for certain projects, exceeding 12000 altogether. The total number includes also, convalescent COVID-19 patients, with comprehensive antibody testing.
Collaboration with OPHTHALMOS Research and Educational Institute archived nearly 2000 volunteers with various eye diagnoses. Molecular diagnostic services showed high-quality testing for inherited kidney and heart conditions, impacting medical and societal issues and benefiting the Ministry of Health's budget.
OpenSpecimen implementation reached full operational capacity in its first phase, with ongoing upgrades.
The project engaged with mass media, presented at conferences, organized educational activities, and received recognition at the 2023 and 2024 Researchers' Night, emphasizing success in genomics, clinical trials, biobanking, and public engagement.
In conclusion, the CY-Biobank project not only achieved milestones but showcased significant progress across diverse fields.
Notably, it delivered 1446 whole exomes of Cypriot volunteers through collaboration with the Regeneron Genetics Center and a private biotech, with plans for additional sample sequencing aiming for a total of 5000. This reflects for the first time a good representation of the Cypriot reference genome, with many potential applications in health and disease.
In the domain of genetic modifiers impacting kidney function, the project is preparing a major manuscript on severe kidney function decline in patients with mutations in COL4A3 and COL4A4 genes. Progress includes a preclinical study on Alport syndrome and detailing more than 300 Cypriot families with suspected inherited heart and kidney conditions, which were referred for genetic investigation.
A groundbreaking clinical trial on MUC1 kidney disease was initiated in two Cypriot cohorts in collaboration with the Broad Institute of MIT and Harvard. Also, the Biobank expanded to nearly 11000 volunteers, plus several hundred follow-up samples for certain projects, exceeding 12000 altogether. The total number includes also, convalescent COVID-19 patients, with comprehensive antibody testing.
Collaboration with OPHTHALMOS Research and Educational Institute archived nearly 2000 volunteers with various eye diagnoses. Molecular diagnostic services showed high-quality testing for inherited kidney and heart conditions, impacting medical and societal issues and benefiting the Ministry of Health's budget.
OpenSpecimen implementation reached full operational capacity in its first phase, with ongoing upgrades.
The project engaged with mass media, presented at conferences, organized educational activities, and received recognition at the 2023 and 2024 Researchers' Night, emphasizing success in genomics, clinical trials, biobanking, and public engagement.
In conclusion, the CY-Biobank project not only achieved milestones but showcased significant progress across diverse fields.
While concrete results are pending, early progress suggests an anticipated significant socio-economic and medical impact from the diagnostic and research projects at the CoE, addressing unmet needs. Chronic kidney disease, affecting over 10% of the population, and inherited heart conditions, affecting about 1/200-250 individuals globally, are being systematically addressed for the first time through extended genetic testing, benefiting Cypriot patients and informing clinicians. The ongoing CYPROME project, having delivered nearly 3000 Whole Exomes of Cypriots, is yielding benefits.
Furthermore, the CoE's infrastructure and expertise are sought by colleagues from UCY and other universities, expanding visibility and participation in external research. Two major collaborations show promise: an expanded agreement with the Regeneron Genetics Center aims to offer over five thousand whole exomes of the general population and for various diseases, and a longstanding partnership with the Broad Institute on MUC1 kidney disease is progressing toward a clinical trial involving Cypriot patients. Finally, amongst others, a landmark publication (2025, in Press) in the best kidney journal, Kidney International, reflects the hard innovative work of colleagues at the CoE, in finding more effective treatments for Alport spectrum disease. This was the result of a preclinical trial in a mouse model for Alport syndrome.
In projecting into the near future, the analysis of the available exomes through the CYPROME project, is already delivering critical information on the genetic morbid anatomy of Cypriots. A diligent study of 1446 exomes with several in silico instruments, has revealed that more than 2.6% of Cypriots have inherited actionable pathogenic/likely pathogenic DNA variants, which upon their knowledge people can act for prevention or amelioration of symptoms and disease outcome.
Finally, the introduction of systematic genetic testing, as a center of reference for inherited kidney and heart conditions, already has shaped the field as many patients and families that remained undiagnosed for decades, are now finding a resolution and an end to their diagnostic odyssey, while also saving substantial funds to the government.
Furthermore, the CoE's infrastructure and expertise are sought by colleagues from UCY and other universities, expanding visibility and participation in external research. Two major collaborations show promise: an expanded agreement with the Regeneron Genetics Center aims to offer over five thousand whole exomes of the general population and for various diseases, and a longstanding partnership with the Broad Institute on MUC1 kidney disease is progressing toward a clinical trial involving Cypriot patients. Finally, amongst others, a landmark publication (2025, in Press) in the best kidney journal, Kidney International, reflects the hard innovative work of colleagues at the CoE, in finding more effective treatments for Alport spectrum disease. This was the result of a preclinical trial in a mouse model for Alport syndrome.
In projecting into the near future, the analysis of the available exomes through the CYPROME project, is already delivering critical information on the genetic morbid anatomy of Cypriots. A diligent study of 1446 exomes with several in silico instruments, has revealed that more than 2.6% of Cypriots have inherited actionable pathogenic/likely pathogenic DNA variants, which upon their knowledge people can act for prevention or amelioration of symptoms and disease outcome.
Finally, the introduction of systematic genetic testing, as a center of reference for inherited kidney and heart conditions, already has shaped the field as many patients and families that remained undiagnosed for decades, are now finding a resolution and an end to their diagnostic odyssey, while also saving substantial funds to the government.