Periodic Reporting for period 3 - SciFiMed (Screening of inFlammation to enable personalized Medicine)
Reporting period: 2023-07-01 to 2025-06-30
A strong and effective immune system is needed for a long, healthy life. Our immune system fends off and fights infections but needs to be in balance to prevent excessive inflammation and autoimmune diseases. Critical in maintaining this balance is the complement system, a central part of our immune system. Within the complement system, a group of closely related proteins, known as the factor H (FH) protein family, orchestrates regulation and activation, thereby maintaining balance. Imbalance within this family is associated with a wide range of both common and rare diseases, affecting various organs and tissues throughout the body, such as the eyes and the kidneys. SciFiMed set out to address two major challenges regarding the FH family: 1) the exact mechanisms of how dysregulation of the FH family contributes to disease are unknown, and 2) there was a lack of easy-to-use and widely available, accurate research and diagnostic tools for determining the levels and function of the FH family.
By providing a solution to these fundamental challenges, SciFiMed aimed to improve diagnostics for diseases associated with dysregulation of the immune system and to enable personalized medicine for incurable (or difficult-to-treat) diseases. With this vision in mind, SciFiMed explored the contribution of the FH protein family to maintain a balanced immune system. To this end, we developed and characterized current and novel research tools targeting the FH family, validating them across labs and providing them in a standardized format. Furthermore, we envisioned a novel handheld biosensor to combine both quantitative and functional activity assessments of the FH family.
By providing a solution to these fundamental challenges, SciFiMed aimed to improve diagnostics for diseases associated with dysregulation of the immune system and to enable personalized medicine for incurable (or difficult-to-treat) diseases. With this vision in mind, SciFiMed explored the contribution of the FH protein family to maintain a balanced immune system. To this end, we developed and characterized current and novel research tools targeting the FH family, validating them across labs and providing them in a standardized format. Furthermore, we envisioned a novel handheld biosensor to combine both quantitative and functional activity assessments of the FH family.
SciFiMed contributed to the state of the art and advanced in the following fields.
>>We generated and validated recombinant FH protein family members, which will ensure reliability and reproducibility of complement and FH protein family-related research.
>> We generated new specific antibodies against FH family members and used these antibodies to optimize and develop four new immunoassays. The assays were produced in a standardized manner by one of our partners, and cross-validated across all research labs part of SciFiMed, demonstrating a high quality, reproducibility and accuracy of each.
>>The developed immunoassays have been successfully launched to the market in 2024 as research use only kits, together with unique, specific antibodies for four FHR proteins.
>>We identified binding partners of distinct FH family members and used these to develop novel tools to study the function of the FH protein family.
>> We developed novel assays to determine the overall functional activity of the complement system, as well as a specific FH functional assay, that is easy-to-use, inexpensive and up-scalable. This will make currently used unreliable and animal-hostile erythrocytes-based activity assays obsolete.
>> We established proof-of-principle of an innovative multiplex lateral flow assay allowing simultaneous quantification of FHR proteins. This novel method allows for rapid detection while requiring minimal volume and is a critical technical advancement towards our envisioned multiplex biosensor.
>> Using the new reagents and tools developed during the project, several new insights in FH protein biology were achieved:
1) for the first time, all FH protein family members were specifically measured in a single cohort of healthy donors, establishing normal ranges and physiological ratios, linked to common genetic variations found in the population;
2) novel disease-associated variants of FHR proteins were identified and functionally characterized;
3) complement regulatory activity of FHR proteins was further refined;
4) the presence of FHR proteins in different body fluids (besides blood plasma) was demonstrated;
5) disease-associated changes in circulating and local tissue concentrations were identified across different disease cohorts, shedding light on the role of the FH protein family in diseases;
6) new physiological binding ligands were identified for each protein, guiding new research into their in vivo function.
Overall, these achievements contribute significantly to our understanding of the FH protein family and their implications in disease. By overcoming challenges and making important discoveries, SciFiMed moves closer to the goal of enabling personalized medicine with the promise to make a change to healthcare.
In summary, SciFiMed successfully completed all eight work package-related objectives, providing 41 deliverables and achieving three major milestones. The results have thus far been presented via 36 posters and 32 oral presentations at various (inter)national scientific meetings and conferences, published in fifteen open access research articles, and have already led to one patent application, with more anticipated in the near future.
>>We generated and validated recombinant FH protein family members, which will ensure reliability and reproducibility of complement and FH protein family-related research.
>> We generated new specific antibodies against FH family members and used these antibodies to optimize and develop four new immunoassays. The assays were produced in a standardized manner by one of our partners, and cross-validated across all research labs part of SciFiMed, demonstrating a high quality, reproducibility and accuracy of each.
>>The developed immunoassays have been successfully launched to the market in 2024 as research use only kits, together with unique, specific antibodies for four FHR proteins.
>>We identified binding partners of distinct FH family members and used these to develop novel tools to study the function of the FH protein family.
>> We developed novel assays to determine the overall functional activity of the complement system, as well as a specific FH functional assay, that is easy-to-use, inexpensive and up-scalable. This will make currently used unreliable and animal-hostile erythrocytes-based activity assays obsolete.
>> We established proof-of-principle of an innovative multiplex lateral flow assay allowing simultaneous quantification of FHR proteins. This novel method allows for rapid detection while requiring minimal volume and is a critical technical advancement towards our envisioned multiplex biosensor.
>> Using the new reagents and tools developed during the project, several new insights in FH protein biology were achieved:
1) for the first time, all FH protein family members were specifically measured in a single cohort of healthy donors, establishing normal ranges and physiological ratios, linked to common genetic variations found in the population;
2) novel disease-associated variants of FHR proteins were identified and functionally characterized;
3) complement regulatory activity of FHR proteins was further refined;
4) the presence of FHR proteins in different body fluids (besides blood plasma) was demonstrated;
5) disease-associated changes in circulating and local tissue concentrations were identified across different disease cohorts, shedding light on the role of the FH protein family in diseases;
6) new physiological binding ligands were identified for each protein, guiding new research into their in vivo function.
Overall, these achievements contribute significantly to our understanding of the FH protein family and their implications in disease. By overcoming challenges and making important discoveries, SciFiMed moves closer to the goal of enabling personalized medicine with the promise to make a change to healthcare.
In summary, SciFiMed successfully completed all eight work package-related objectives, providing 41 deliverables and achieving three major milestones. The results have thus far been presented via 36 posters and 32 oral presentations at various (inter)national scientific meetings and conferences, published in fifteen open access research articles, and have already led to one patent application, with more anticipated in the near future.
SciFiMed has made significant strides beyond the current state of the art by developing and making available novel tools to measure levels and the functional activity of the complement system through platform technologies that will provide relevant information and are easy to use. This innovation allows for the accurate detection of disruptions in the complement system, surpassing existing assays and methods. Additionally, our collaborative efforts have resulted in the discovery of potential novel ligands of the FH protein family, providing insights into the mechanisms by which the FH family contributes to disease.
We launched four new immunoassays that support standardization in measuring the FH protein family throughout the field, and achieved proof-of-principle for next-generation rapid detection methods towards potential diagnostic use.
The successful deployment of our novel tools holds the potential to significantly enhance the management of complement-associated diseases through improved risk assessment of disease, disease diagnosis, and more accurate predictions of disease progression. This, in turn, can lead to earlier interventions and improved patient outcomes. Furthermore, with the expanding landscape of therapeutic complement inhibitors, our novel tools hold promise in aiding in predicting treatment responses and guide personalized medicine. Moreover, the gained insight into the pathophysiology of the FH family in disease as well as the new research tools developed and made available will promote and enable the discovery of new tailored interventions for these difficult to treat complement-associated diseases.
We launched four new immunoassays that support standardization in measuring the FH protein family throughout the field, and achieved proof-of-principle for next-generation rapid detection methods towards potential diagnostic use.
The successful deployment of our novel tools holds the potential to significantly enhance the management of complement-associated diseases through improved risk assessment of disease, disease diagnosis, and more accurate predictions of disease progression. This, in turn, can lead to earlier interventions and improved patient outcomes. Furthermore, with the expanding landscape of therapeutic complement inhibitors, our novel tools hold promise in aiding in predicting treatment responses and guide personalized medicine. Moreover, the gained insight into the pathophysiology of the FH family in disease as well as the new research tools developed and made available will promote and enable the discovery of new tailored interventions for these difficult to treat complement-associated diseases.