FAP neuropathy and emerging treatments.
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).
APHP, HUPS, Univ Paris Sud, le Kremlin Bicêtre Cedex, France, david.adams@bct.aphp.fr.
David
D
Adams
Marie
M
Théaudin
Cecile
C
Cauquil
Vincent
V
Algalarrondo
Michel
M
Slama
D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000378:metabolism / Q000628:therapy*; D000818:Animals; D001583:Benzoxazoles / Q000627:therapeutic use*; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D016031:Liver Transplantation; D009154:Mutation / Q000235:genetics*; D011228:Prealbumin / Q000378:metabolism*
D001583:Benzoxazoles; D011228:Prealbumin; C547076:tafamidis