Liver transplantation has been considered as a promising
therapy to halt the progression of clinical symptoms in familial amyloidotic
polyneuropathy (FAP) because most
transthyretin (TTR) is produced by the liver. In addition, domino
liver transplantation using an FAP patient's liver has been performed because of a shortage of donor livers. However, because the use of
liver transplantation as
therapy for FAP has given rise to several problems, an alternative treatment is needed. We have tried several other approaches. Recent studies suggested that certain
metal ions affect amyloidogenesis. Among
metal ions tested in an in vitro
amyloid formation study, Cr3+ increased stability of both normal and mutant TTR tetramers and suppressed TTR amyloidogenesis induced by low pH. Our findings indicate that Cr3+ acts to suppress TTR amyloidogenesis. BSB, a
Congo red derivative that binds to
amyloid fibrils in FAP as well as to those in
senile plaques in
Alzheimer's disease, effectively suppressed TTR
amyloid formation in vitro. BSB may thus be useful for preventing
amyloid formation.
Free radical scavenger therapy was also tried in FAP patients but yielded no conclusive results. Immunization for transgenic mice having the ATTR V30M gene using ATTR Y78P resulted in suppression of
amyloid deposits. Finally, an
RNA/
DNA chimera and single-stranded
oligonucleotides (SSOs) were tested in vitro and in vivo in an attempt to repair the amyloidogenic TTR gene in the liver and retina. On the basis of results achieved so far, SSO is a promising tool for gene therapy.