Periodic Reporting for period 2 - SciFiMed (Screening of inFlammation to enable personalized Medicine)
Período documentado: 2022-01-01 hasta 2023-06-30
The pandemic of the coronavirus disease 2019 (COVID-19) has underscored the extreme importance of having a strong and effective immune system. On one hand, the immune system plays a critical role in preventing and fighting infections, while its disruption causes inflammation and autoimmune diseases, highlighting the need to maintain a balanced immune system. A group of seven proteins of the immune system, called the Factor H (FH) protein family, plays a critical role in the immune system’s balance, and consequently, issues with the FH family are linked to a variety of diseases. The biggest hurdles in dealing with these diseases are related to two issues: 1) the exact mechanisms of how dysregulation of the FH family contributes to disease are unknown, and 2) there's a lack of easy-to-use and widely available accurate diagnostic methods for determining the levels and function of the FH family.
The goal of SciFiMed is to provide a solution to this overarching challenge to improve diagnostics for diseases associated with a dysregulation of the immune system and to enable personalized medicine for incurable (or difficult-to-treat) diseases. With this vision in mind, SciFiMed will explore the contribution of the FH protein family to maintain a balanced immune system. Furthermore, we will develop a novel handheld biosensor to combine both quantitative and functional activity assessments of the FH family, none of which has been done before. In the future, the multiplexed on-site biosensor with inherent functionality testing, can become an invaluable tool for doctors and medical personnel in aiding patients with these diseases and facilitating personalized medicine.
The goal of SciFiMed is to provide a solution to this overarching challenge to improve diagnostics for diseases associated with a dysregulation of the immune system and to enable personalized medicine for incurable (or difficult-to-treat) diseases. With this vision in mind, SciFiMed will explore the contribution of the FH protein family to maintain a balanced immune system. Furthermore, we will develop a novel handheld biosensor to combine both quantitative and functional activity assessments of the FH family, none of which has been done before. In the future, the multiplexed on-site biosensor with inherent functionality testing, can become an invaluable tool for doctors and medical personnel in aiding patients with these diseases and facilitating personalized medicine.
SciFiMed contributed to the state of the art and advanced in the following fields in the 1st reporting period:
>>SciFiMed generated and validated recombinant FH protein family members, which will ensure reliability and reproducibility of complement and FH protein family-related research.
>> SciFiMed generated specific antibodies against FH family members and used these antibodies successfully in a first pilot study for developing diagnostic assays capable of quantifying FH family members in a reliable manner. This is the preliminary stage to provide specific, easily performable quantitative assays for all FH-family members and establishing a multiplex assay.
>> SciFiMed identified binding partners of distinct FH family members. These new probes are the first step to answer the controversial question: What are the ligands of the FH-family and do they regulate inflammation?
>> SciFiMed developed novel assays to determine the overall functional activity of the complement system that are easy-to-use, inexpensive and up-scalable. This will make currently used unreliable and animal-hostile erythrocytes-based activity assays obsolete.
>> SciFiMed designed an innovative multiplex lateral flow assay. This proof-of-principle will open new doors in diagnostic developments. This technology could be applied to detect a variety of multiple analytes in parallel within one device.
During the 2nd reporting period, SciFiMed advanced its progress by focusing its strategy on specific proteins within the FH protein family. This targeted approach was necessary due to the numerous accomplishments achieved in the first phase, the project's comprehensive scope, and the diverse potential avenues for future exploration. Consequently, the 2nd reporting period yielded noteworthy achievements in both quantification and functional assay development endeavors:
Quantification Projects:
>> Characterized and validated monoclonal antibodies for the specific detection of the FH protein family were developed and are set to be released commercially in the near future. This initiative will ensure the availability of these valuable research tools.
>> Collaborative efforts resulted in the development of enzyme-linked immune assay (ELISA) tests for FH-related (FHR)-2, FHR-3, FHR-4, and FHR-5 proteins. These tests will undergo intensive validation within the consortium and will be made accessible to third parties outside of SciFiMed from next year.
>> To optimize detection efficacy, the ELISA tests were adapted into rapid detection formats, resulting in the development of the pioneering lateral flow assay for FHRs. This innovative assay enables quick and simultaneous detection of three FHRs (FHR-2/3/5) from a single sample.
Functional Projects:
>> The identification of specific ligands for the FHR proteins was a significant milestone achieved. Complementary methods were utilized to shed light on the complex interactions between these proteins and other molecules. The identified ligands are currently undergoing validation to confirm their specificity and functionality.
>> During the validation process, it was discovered that commercially available recombinant proteins with a His-tag exhibited non-specific interactions with some of the binding partners. Addressing this challenge, the focus shifted towards the generation/production of FHR proteins without tags.
>> Functional assays capable of detecting the activity of different complement pathways were developed and further validated.
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 progressed on all eight work package-related objectives, provided eleven deliverables, and accomplished one milestone in the past eighteen months.
>>SciFiMed generated and validated recombinant FH protein family members, which will ensure reliability and reproducibility of complement and FH protein family-related research.
>> SciFiMed generated specific antibodies against FH family members and used these antibodies successfully in a first pilot study for developing diagnostic assays capable of quantifying FH family members in a reliable manner. This is the preliminary stage to provide specific, easily performable quantitative assays for all FH-family members and establishing a multiplex assay.
>> SciFiMed identified binding partners of distinct FH family members. These new probes are the first step to answer the controversial question: What are the ligands of the FH-family and do they regulate inflammation?
>> SciFiMed developed novel assays to determine the overall functional activity of the complement system that are easy-to-use, inexpensive and up-scalable. This will make currently used unreliable and animal-hostile erythrocytes-based activity assays obsolete.
>> SciFiMed designed an innovative multiplex lateral flow assay. This proof-of-principle will open new doors in diagnostic developments. This technology could be applied to detect a variety of multiple analytes in parallel within one device.
During the 2nd reporting period, SciFiMed advanced its progress by focusing its strategy on specific proteins within the FH protein family. This targeted approach was necessary due to the numerous accomplishments achieved in the first phase, the project's comprehensive scope, and the diverse potential avenues for future exploration. Consequently, the 2nd reporting period yielded noteworthy achievements in both quantification and functional assay development endeavors:
Quantification Projects:
>> Characterized and validated monoclonal antibodies for the specific detection of the FH protein family were developed and are set to be released commercially in the near future. This initiative will ensure the availability of these valuable research tools.
>> Collaborative efforts resulted in the development of enzyme-linked immune assay (ELISA) tests for FH-related (FHR)-2, FHR-3, FHR-4, and FHR-5 proteins. These tests will undergo intensive validation within the consortium and will be made accessible to third parties outside of SciFiMed from next year.
>> To optimize detection efficacy, the ELISA tests were adapted into rapid detection formats, resulting in the development of the pioneering lateral flow assay for FHRs. This innovative assay enables quick and simultaneous detection of three FHRs (FHR-2/3/5) from a single sample.
Functional Projects:
>> The identification of specific ligands for the FHR proteins was a significant milestone achieved. Complementary methods were utilized to shed light on the complex interactions between these proteins and other molecules. The identified ligands are currently undergoing validation to confirm their specificity and functionality.
>> During the validation process, it was discovered that commercially available recombinant proteins with a His-tag exhibited non-specific interactions with some of the binding partners. Addressing this challenge, the focus shifted towards the generation/production of FHR proteins without tags.
>> Functional assays capable of detecting the activity of different complement pathways were developed and further validated.
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 progressed on all eight work package-related objectives, provided eleven deliverables, and accomplished one milestone in the past eighteen months.
SciFiMed has made significant strides beyond the current state of the art by developing novel tools to measure levels and 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.
Upon the project's completion, we envision the availability of multiple commercially research assay. These innovations will possess the capability to measure both levels and functionality of the FH protein family as well as the complement system. Additionally, our research is poised to yield an array of novel research tools dedicated to the FH protein family.
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. 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 a new tailored interventions for these difficult to treat complement-associated diseases.
Upon the project's completion, we envision the availability of multiple commercially research assay. These innovations will possess the capability to measure both levels and functionality of the FH protein family as well as the complement system. Additionally, our research is poised to yield an array of novel research tools dedicated to the FH protein family.
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. 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 a new tailored interventions for these difficult to treat complement-associated diseases.