Periodic Reporting for period 3 - PoCOsteo (PoC in-office device for identifying individuals at high risk of Osteoporosis and osteoporotic fracture)
Periodo di rendicontazione: 2020-10-01 al 2022-03-31
Osteoporosis is the most frequently found metabolic bone disease and is characterized by low bone mass, micro-architectural bone deterioration, and increased bone fragility and fracture risk.
Early detection of individuals at risk of osteoporosis and starting a suitable treatment before the presentation of the complications would drastically improve the current situation.
In order to determine the effective onset of osteoporosis in an early stage in individuals predicted to be at risk, and to accurately monitor the evolution during treatment, the analysis of Bone Turnover Markers (BTMs) is emerging as a key route that could provide the required sensitivity/specificity. However, the routine use of BTMs in clinical practice is complicated by large random within-patient variability and biologic variability.
The alternatives to BTM analysis such as DXA or ultrasonic measurements are expensive for smaller hospitals or private practices and/or lack sensitivity.
However, with today’s technological advances, we believe it is possible to develop an in-office device capable of determining both the genetic predisposition and BTM values from a single drop of blood, at acceptable cost.
In order to develop such a device, various technologies come together. While the proof of concept of different parts of the final device are already designed in the lab, their integration into a single device is still an idea and thus further tests are needed to confirm its accuracy for the final application.
The PoCOsteo project thus aims to integrate proteomics and genomics technology into a functional single PoC device and to validate the final instrument by comparing the results with that of the current state-of-the-art of each technology separately. The final device is aimed to be used by the physicians to identify individuals at high-risk of osteoporosis and osteoporotic fracture, to provide them with personalized care, and monitor the treatment process more efficiently.
In summary, the overall aim of PoCOsteo is the development, clinical validation and preparation for commercialisation of a Point-of-Care tool for bone disease (a.o. osteoporosis) prevention, detection and treatment.
Early detection of individuals at risk of osteoporosis and starting a suitable treatment before the presentation of the complications would drastically improve the current situation.
In order to determine the effective onset of osteoporosis in an early stage in individuals predicted to be at risk, and to accurately monitor the evolution during treatment, the analysis of Bone Turnover Markers (BTMs) is emerging as a key route that could provide the required sensitivity/specificity. However, the routine use of BTMs in clinical practice is complicated by large random within-patient variability and biologic variability.
The alternatives to BTM analysis such as DXA or ultrasonic measurements are expensive for smaller hospitals or private practices and/or lack sensitivity.
However, with today’s technological advances, we believe it is possible to develop an in-office device capable of determining both the genetic predisposition and BTM values from a single drop of blood, at acceptable cost.
In order to develop such a device, various technologies come together. While the proof of concept of different parts of the final device are already designed in the lab, their integration into a single device is still an idea and thus further tests are needed to confirm its accuracy for the final application.
The PoCOsteo project thus aims to integrate proteomics and genomics technology into a functional single PoC device and to validate the final instrument by comparing the results with that of the current state-of-the-art of each technology separately. The final device is aimed to be used by the physicians to identify individuals at high-risk of osteoporosis and osteoporotic fracture, to provide them with personalized care, and monitor the treatment process more efficiently.
In summary, the overall aim of PoCOsteo is the development, clinical validation and preparation for commercialisation of a Point-of-Care tool for bone disease (a.o. osteoporosis) prevention, detection and treatment.
In order to have a framework of the musts and limitations for the final device, a list of all prerequisites that should be considered in the final device, both from end-costumers and regulatories point of view, along with the technological conditions for each partner was made.
The next step was to develop the proteomic and genomic biosensors and corresponding microfluidic manifolds. The latter was designed in a way that the least amount of blood, collected through fingerprick, is needed.
Based on the outcome of the proteomic and genomic biosensor development phase, two cartridges were designed and developed for the measurement of BTMs and genetic profile in a single drop of blood from fingerprick. These cartridges consisted of the corresponding proteomic and genomic biosensor and a microfluidic manifold to allow the flow of small amount of blood and reagents in the microsystem. After production the cartridges were packed to increase the shelf-life of the cartridges.
The final device with an integrated potentiostat has been finalized taking into account all prerequisites, both from end-costumers and regulatories point of view, along with the technological conditions for each partner. It was designed to be portable, user-friendly and answer the needs of both biosensors in different steps of sample preparation, measurement and reporting.
The next step was to validate and test the cartridges as well as the device and the potentiostat. The primary results showed the proteomic cartridge to be reproducible and accurate in measuring the target BTMs. The cartridge was also tested with the device and similar results were achieved. The device potentiostat (LabStat) was also validated using the commercial Autolab which also showed somehow comparable results and certain advantages for the LabStat, including simultaneous measurement of up to 64 electrodes in a couple of seconds. The device itself was also successful in finalizing all the tasks needed for sample preparation and testing when genomic cartridge was used.
As it was the objective to test the device in practice, two clinical studies have been designed and ethically approved. These studies were meant to be conducted in Austria (European population) and Iran (Middle Eastern population). The participants have been recruited and followed in the course of the project based on the submitted protocol. At the same time preliminary modeling simulations have been performed in order to have a better understanding of the needed variables and also the modeling techniques for the later clinical validation phases.
However, considering the delays due to the COVID 19 pandemic and BREXIT, it was, unfortunately, not possible to finalize the lab validation step in time and send the device to the clinical partners for final clinical validation before the contractual end of the PoCOsteo project, and this while the data of the clinical studies conducted in the past 4,5 years resulted in a new modeling simulation that might help with better prediction of fracture and osteoporosis.
The next step was to develop the proteomic and genomic biosensors and corresponding microfluidic manifolds. The latter was designed in a way that the least amount of blood, collected through fingerprick, is needed.
Based on the outcome of the proteomic and genomic biosensor development phase, two cartridges were designed and developed for the measurement of BTMs and genetic profile in a single drop of blood from fingerprick. These cartridges consisted of the corresponding proteomic and genomic biosensor and a microfluidic manifold to allow the flow of small amount of blood and reagents in the microsystem. After production the cartridges were packed to increase the shelf-life of the cartridges.
The final device with an integrated potentiostat has been finalized taking into account all prerequisites, both from end-costumers and regulatories point of view, along with the technological conditions for each partner. It was designed to be portable, user-friendly and answer the needs of both biosensors in different steps of sample preparation, measurement and reporting.
The next step was to validate and test the cartridges as well as the device and the potentiostat. The primary results showed the proteomic cartridge to be reproducible and accurate in measuring the target BTMs. The cartridge was also tested with the device and similar results were achieved. The device potentiostat (LabStat) was also validated using the commercial Autolab which also showed somehow comparable results and certain advantages for the LabStat, including simultaneous measurement of up to 64 electrodes in a couple of seconds. The device itself was also successful in finalizing all the tasks needed for sample preparation and testing when genomic cartridge was used.
As it was the objective to test the device in practice, two clinical studies have been designed and ethically approved. These studies were meant to be conducted in Austria (European population) and Iran (Middle Eastern population). The participants have been recruited and followed in the course of the project based on the submitted protocol. At the same time preliminary modeling simulations have been performed in order to have a better understanding of the needed variables and also the modeling techniques for the later clinical validation phases.
However, considering the delays due to the COVID 19 pandemic and BREXIT, it was, unfortunately, not possible to finalize the lab validation step in time and send the device to the clinical partners for final clinical validation before the contractual end of the PoCOsteo project, and this while the data of the clinical studies conducted in the past 4,5 years resulted in a new modeling simulation that might help with better prediction of fracture and osteoporosis.
With ageing society, osteoporosis is emerging as one of the main diseases that, indirectly via fractures, impacts significantly the quality of life on the one hand and healthcare expenses on the other. Because it is a ‘silent disease’ which really only manifests itself in the excessive consequences of a fall, both the diagnosis and compliance to therapy later on are problematic, contributing to a huge treatment gap and related costs both financially and in terms of quality of life. The only way to effectively change this situation is by providing the medical community with accurate diagnostic tools that are easily accessible and easy to use, provide immediate feedback, and are low-cost, both in terms of capex and opex. By combining in PoCOsteo a genomic and a proteomic assessment in one finger prick test, we will offer a unique tool which can in a single low-cost test make a convincing assessment of this important disease. This will allow the physician to immediately define follow-up actions with the patients, without having to schedule dedicated follow-up meetings which are costly and often lead to patient drop out.
The advanced requirements of the osteoporosis use case will drive a close collaboration between various players in the proposed value chain. The need to integrate all technology elements into a working set-up sufficiently advanced so that it can be used and evaluated during the project by non-technical people in medical labs, will require all parties to work together towards pragmatic and stable solutions, with commercial value that can be exploited also in other use cases after PoCOsteo. As such we expect PoCOsteo will lead to important new technology elements which will become commercially available.
Planned support and advise of the project by the International Osteoporosis Foundation, being the main global alliance of patient societies, research organizations, healthcare professionals and international companies working to promote bone, muscle and joint health, will ensure close follow-up and adjustment of regulatory issues, related to the project work plan and the later use of the PoCOsteo tool in realistic environments.
The advanced requirements of the osteoporosis use case will drive a close collaboration between various players in the proposed value chain. The need to integrate all technology elements into a working set-up sufficiently advanced so that it can be used and evaluated during the project by non-technical people in medical labs, will require all parties to work together towards pragmatic and stable solutions, with commercial value that can be exploited also in other use cases after PoCOsteo. As such we expect PoCOsteo will lead to important new technology elements which will become commercially available.
Planned support and advise of the project by the International Osteoporosis Foundation, being the main global alliance of patient societies, research organizations, healthcare professionals and international companies working to promote bone, muscle and joint health, will ensure close follow-up and adjustment of regulatory issues, related to the project work plan and the later use of the PoCOsteo tool in realistic environments.