FAP neuropathy and emerging treatments

Curr Neurol Neurosci Rep. 2014 Mar;14(3):435. doi: 10.1007/s11910-013-0435-3.


Transthyretin familial amyloid polyneuropathy (TTR-FAP) classically presents as a length dependent small fiber polyneuropathy in endemic countries like Portugal. In nonendemic countries, it may mimic a variety of chronic polyneuropathies, with several phenotypes: ataxic, upper limb onset neuropathy, or motor. In these cases, there is usually a late onset and no positive family history. TTR gene sequencing appears the most pertinent first-line test for diagnosis. Cardiac involvement of various severities is common in FAP. Liver transplantation remains the standard antiamyloid therapy with better results in Val30Met TTR-FAP of early onset. Antiamyloid medication has been developed. (1) TTR stabilizers: Tafamidis was the first drug approved in Europe in stage 1 (walking unaided) TTR-FAP to slow progression of the disease; diflunisal has been assessed in a phase 3 clinical trial; (2) TTR gene silencing is a new strategy to inhibit production of both mutant and nonmutant TTR with antisense oligonucleotides or SiRNA (2 ongoing phase 3 clinical trials).

Publication types

  • Review

MeSH terms

  • Amyloid Neuropathies, Familial / diagnosis
  • Amyloid Neuropathies, Familial / metabolism
  • Amyloid Neuropathies, Familial / therapy*
  • Animals
  • Benzoxazoles / therapeutic use*
  • Gene Silencing / physiology
  • Humans
  • Liver Transplantation*
  • Mutation / genetics*
  • Prealbumin / metabolism*


  • Benzoxazoles
  • Prealbumin
  • tafamidis

Supplementary concepts

  • Amyloidosis, Hereditary, Transthyretin-Related