Models of AL amyloidosis for a better understanding of the disease and therapeutic investigations – ModAL

AL amyloidosis is a rare but devastating disease caused by the tissue/organ deposition of amyloid fibrils composed of a monoclonal immunoglobulin light chain (LC). Despite extensive biochemical studies and clinical investigations, the pathophysiology of this disease is still misunderstood due to the absence of a reliable animal model. We have recently uncovered for the first time the conditions to reproduce AL amyloidosis in a proprietary transgenic mouse model. In the present project, we will use this original and unique animal model to better understand the events leading to in vivo fibril formation, the intrinsic toxicity of amyloid LC and their effects on different biological processes, including impaired hemostasis. We will also take advantage on this long-awaited model to validate two complementary approaches aiming at removing AL amyloid deposits from organs.