Encouraging impact of doxycycline on early mortality in cardiac light chain (AL) amyloidosis

Early mortality in cardiac light chain (AL) amyloidosis has not changed substantially over the last 25 years, although long term outcomes have improved. 1 In addition to the physical effects of AL fibril deposition causing cardiac dysfunction, amyloidogenic light chains are cardiotoxic, reducing contractility in cardiac myocytes, 2 causing early death in zebra fish 3 and reducing pharyngeal contractility in C.elegans . 4 Blocking light chain cardiotoxicity by small molecules is attractive. Doxycycline interferes with amyloid fibril formation in a mouse model of AL amyloidosis 5 and abrogates light chain toxicity in vitro . 4 Doxycycline combined with tauroursodeoxycholic acid improved cardiac outcomes in transthyretin amyloidosis. In a cohort of patients with systemic AL amyloidosis, doxycycline given as antimicrobial prophylaxis post autologous stem cell transplantation significantly improved survival compared to controls who were given penicillin. 6 We and others reported that treatment with highly effective bortezomib-based chemotherapy does not improve early survival in AL amyloidosis. 7 , 8 Hence, an agent that directly interferes with the amyloidogenic pathway targeting either misfolded light chains or the amyloid fibrils is needed.