Effect of liver trasplantation on familial amyloidotic polyneuropathy (FAP) and its limt

Abstract

Familial amyloidotic polyneuropathy (FAP) is a hereditary intractable disease induced by mutated transthyretin (TTR). Since TTR is predominantly synthesized by liver, liver transplantation has been performed to halt the clinical symptoms of FAP in the worldwide. It has been well documented that liver transplantation could halt the progression of FAP manifestations. However, the surgery could not prevent ocular symptoms and in some cases, cardiopathy and neuroparthy progressed even after liver trasplantation. Quantitative analyses for changes in the amount of amyloid deposition and ratio of wild type and variant type of TTR for autopsy transplanted FAP cases revealed that the amount of amyloid deposition decreased in most of the organs, but in heart and lung, the amount increased even after liver transplantation. In those organs, the ratio of wild type to variant TTR increased. Since liver transplantation has several problems, we are now performing several new therapeutic researches for FAP, such as development of drug stabilizing tetrameric form of TTR, siRNA therapy to stop TTR production, and low molecular compounds for preventing misfolding of TTR.