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Report

Teaser, summary, work performed and final results

Periodic Reporting for period 1 - RELEVANCE (Regulation of red cell life-span, erythropoiesis, survival, senescence and clearance)

Teaser

Summary

This project addresses several global problems related to (i) the diagnoses and personalized treatment of patients with rare anemia, (ii) culturing of red blood cells to expand the stored pool of red cells for transfusion, (iii) optimization of the outcome of transfusion, and (iv) the impact of moderate and extreme endurance exercise on red blood cell turnover. The total number of patients with rare forms of hereditary anemia such as sickle cell disease, thalassemia and others exceeds a million worldwide. Most of these patients are from African, south American and Asian countries with low income and limited access to expensive therapies and complex therapeutic interventions. Within this project we focus on development of robust and inexpensive solutions for diagnosis and assessment of disease severity. We also work towards development of inexpensive and efficient supportive therapies involving off-label use of known off-patent compounds to be introduced globally.
We are a team of 13 partners from 7 countries hosting 15 early stage researchers (ESRs) that comes together to address these challenges. Our project gives unique training opportunities for the ESRs that are exposed to multidisciplinary training in academic, industrial and clinical environment during the projectâ€™s life-time. Secondments and close interaction between the partners multiply the power of each group manifolds increasing the quality of research and allowing immediate translation between bed, bench and machine-building workshop. All ideas coming from researchers that are inspired by the needs of clinical hematologists and may be immediately discussed, evaluated and supported by the industrial partners. This high degree of flexibility and versatility of tools and approaches already resulted in the impressive progress achieved by all project participants. Expected gain by the end of the project includes 15 young experts that will bring the work initiated by the PIs further contributing to the developments in the area.

Work performed

The project was initiated as recruitment round and selection of the best candidates for the appealing tasks to solve was completed. At present, the team of ESRs on the project is actively interacting with each other during training sessions as well as working on individual projects and travelling to the partner-groups for secondments. Inspiration of young people in their work was evident as they reflected on their progress using the â€œword of artâ€ during Silvester contest. By now RELEVANCE is a mature team with close interactions between the partners. Listed below are some examples of the progress we have achieved so far. A group of academic and industrial partners produced the first prototype of a device for quick and effective testing of red cell membrane stability and cell volume abnormalities in blood of patients with rare diseases. At present the prototype is tested for reproducibility and stability of function. In parallel several more devices are under construction for testing by the research and clinical partners. Protocols for high throughput testing of ion transport through the red cell membrane are developed for drug testing. Fundamental mechanisms and markers of severity of disease are identified for patients with hereditary spherocytosis, xerocytosis and sickle cell disease. Together with industrial partners, research groups involved in development of ex vivo red cell production system are making substantial progress in this translational research area. Promising data are obtained for ion transporters as potential pharmacological targets for patients with rare anemia as well as for improvement of the outcome of blood transfusion. Knowledge obtained on responses of red blood cells to moderate exercise and endurance training â€œto the limitâ€ will enable defining of optimal training protocols for sedentary subjects and patients with rare anemia and for endurance athletes. Fundamental mechanisms in control of red cell longevity and ageing are being discovered. Finally, research, clinical and industrial partners profit from having software-producing industrial experts on board solving multiple problems from supporting our web-page to producing of sophisticated self-learning software for red blood cell image analysis.

Final results

Substantial progress beyond the state of the art is being achieved in research on the optimization of the protocols of ex vivo culturing of RBCs from erythroid precursor cells. Academic partners are working towards understanding of the fundamental properties of red cells and the mechanisms regulating their production maturation and ageing as well as on the basic mechanisms of pathologies. Novel markers of disease severity and new potential targets for pharmacological interventions have already been suggested for several rare red cell disorders. Development of novel technologies to support both RBC culturing, assessment of disease severity is on the way. Patents are filed and one of the industrial partners intends to bring the final product based on microfluidic and optical technologies to the market. Protocols for high throughput screening for selection of optimal personalized medication and drug testing are being developed by academic and industrial partners. We are confident that benefits for the SMEs involved in the project will include generation of new technologies and products that currently have no analogues at the global market. Most of the work performed within the project is of clinical relevance and will result in benefits for patientsâ€™ community. Finally, creation of the atmosphere of interest to this research and medical area results inspires our colleagues in Europe and all over the world to join us. The resulting network spreads beyond the consortium and keeps growing as â€œcritical massâ€ is being achieved to drive rapid progress in the field with the center being here, in Europe.