Evaluation of tafamidis as first-line therapeutic agent for transthyretin familial amyloidotic polyneuropathy

摘要: Almost 100 mutations in the human transthyretin (TTR) gene cause autosomal dominant disorders of familial amyloidotic polyneuropathy (FAP) and cardiomyopathy. While these have been clinically classified as separate disorders, peripheral autonomic nervous systems heart are frequently involved same patient. Deposition amyloid derived from a kinetically or thermodynamically unstable mutant TTR precursor produces an ascending sensorimotor with marked involvement. Since 1990, treatment has liver transplantation donor carrying two wild-type genes, providing crude form therapy. Multiple studies shown that small molecules fitting T4-binding pocket can stabilize molecule, reducing its capacity to release fibril precursor. Tafamidis is first molecule be tested placebo-controlled trial patients TTR-associated FAP. did not achieve primary endpoints, it vivo had favorable effect on some aspects disease progression, particularly when administered early course. It may represent alternative transplantation, related V30M mutation. Longer-term required determine whether represents stabilizing remittive treatment.