[Analyses of pathogenesis and therapeutic approaches for hereditary amyloidosis]

Amyloidosis is a disorder of protein metabolism in which normally soluble autologous proteins are deposited in tissues as abnormal insoluble fibrils, causing structural and functional disruptions. We have recently identified the novel localized amyloidosis accompanied by trichiasis. The precursor protein of amyloid deposits was mutated lactoferrin and all the patients had lactoferrin Glu561Asp. The disease was classified hereditary amyloidosis whose risk factor is trichiasis. We examined the therapeutic possibilities for mutated transthyretin(ATTR) related familial amyloidotic polyneurpathy(FAP), one of the systemic amyloidoses. Cr3+ suppressed amyloid formation by stabilizing ATTR structure in vitro. BSB is a useful new diagnostic tool to detect amyloid deposits both in in vitro and in vivo and may have therapeutic potential for preventing amyloid deposition. Gene therapy using single-stranded oligonuclotides(SSOs) may become a promising tool for therapy instead of liver transplantation. SSOs with athrocollagen effectively replaced the TTR gene both in vitro and in vivo.