[Analyses of amyloid formation mechanism in familial amyloidotic polyneuropathy and therapeutic trial].

Familial amyloidotic polyneuropathy (FAP) is characterized by systemic accumulation of amyloid fibrils in the peripheral nerves and other organs. FAP ATTR Val30Met is the most common of the familial forms of amyloidosis. In the Kumamoto district, 5 different points of mutation in transthyretin (TTR) have been discovered. To make a diagnosis of FAP, histochemical analysis using ATTR Val30Met monoclonal antibody and FAP patients' hair, and mass spectrometry which can analyze TTR post-translational modifications in the blood circulation and cerebrospinal fluid. From our examinations, oxidative stress and beta protein metabolism is deeply connected with amyloid formation mechanism. Liver transplantation for FAP is only the therapy to save the life of FAP patients. By 1999, we had 17 FAP patients who underwent liver transplantation. They are all alive and showed some improvement predominantly in autonomic dysfunction after the surgery. Liver transplantation revealed that FAP does not progress if the TTR gene in the liver is normalized, suggesting the therapeutic possibility of gene therapy to the liver in FAP patients.