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Establishment of the macrophage production methodology for the development of the cell-based therapy for the eradication of amyloid deposits in AL-amyloidosis
Project IdSGS22/LF/2023
Main solverMUDr. Tereza Popková
Period1/2023 - 12/2023
ProviderSpecifický VŠ výzkum
Statefinished
AnotationPrimary systemic amyloidosis (AL (amyloid light chain) amyloidosis) is a disease caused by clonal proliferation of plasma cells secreting unstable protein products ? light chains of antibodies that cumulatively infiltrate peripheral tissues. Toxic deposits are formed within the infiltrated tissues, which gradually disrupt the function of important structures and organs (especially the heart, kidneys, liver, and peripheral nervous system). The resulting damage has a progressive character, as the natural human immune system is unable to remove protein deposits due to their specific structure. Currently, the treatment of amyloidosis is mainly focused on the eradication of clonal plasma cells producing aberrant protein, but this is not a solution for already formed organ deposits and organ dysfunction. Macrophages are immune cells present throughout all tissues. They are part of the innate immunity, what means they respond promptly whenever they encounter an antigen. Among their specific functions is the ability of phagocytosis - a process during which the macrophage is able to engulf and then intracellularly degrade damaged cells, microbes or foreign particles. The aim of this project is to introduce a methodology for the isolation and differentiation of macrophages from primary cells/cell lines, which in the future can be used to create a therapeutic product consisting of genetically modified macrophages capable of specific recognition and phagocytosis of AL amyloid stored in tissues. This strategy is completely revolutionary in the current concept of treatment and could be a hope for patients with advanced organ damage, whose only treatment option is now organ transplantation.