[Therapeutic strategy for familial amyloid polyneuropathy (FAP)]

Abstract

Familial amyloid polyneuropathy (FAP) was long considered to be an incurable disease, but a new therapeutic approach was developed 15 years ago. As the liver produces most of the transthyretin (TTR) in serum, it was assumed that the replacement of a liver expressing an abnormal TTR gene should stop the production of the variant TTR, the serum amyloid precursor in FAP. Until now about 1,500 FAP patients underwent liver transplantation, and the 10-year-survival rate is about 77%. After operation the progression of FAP symptoms certainly stopped, and patients who were in an early stage of the disease and underwent successful operations showed considerable improvement in their quality of life. Electrophysiological study of peripheral nerve function has demonstrated that liver transplantation can halt the progression of peripheral neuropathy in FAP patients, and histopathological regression of amyloid deposits was seen on the patients with long post-transplatation courses. Pharmacological therapies have been considered for FAP patients and among them, diflunisal, one of non-steroidal antiinflammatory drugs, is very promising. TTR tetramer dissociation is an initial step for the process of TTR-derived amyloid fibril formation associated with FAP and diflinisal can inhibit this process by stabilization of the TTR tetramer. Clinical trial of this drug for FAP patients is now going worldwide.