title: The transthyretin amyloidoses: advances in therapy.
abstract: There are two forms of transthyretin (TTR) amyloidosis: non-hereditary and hereditary. The non-hereditary form (ATTRwt) is caused by native or wild-type TTR and was previously referred to as senile systemic amyloidosis. The hereditary form (ATTRm) is caused by variant TTR which results from a genetic mutation of TTR. The predominant effect of ATTRwt amyloidosis is on the heart, with patients having a greater left ventricular wall thickness at presentation than the devastating form which is light chain (AL) amyloidosis. ATTRm amyloidosis is broadly split into two categories: a type that predominantly affects the nervous system (often called familial amyloid polyneuropathy (FAP)) and one with a predilection for the heart (often called familial amyloid cardiomyopathy (FAC)). Approximately half of all TTR mutations known to express a clinical phenotype cause a cardiomyopathy. Since the introduction of orthotopic liver transplantation for ATTRm amyloidosis in 1991, several additional therapies have been developed. These therapies aim to provide a reduction or elimination of TTR from the plasma (through genetic approaches), stabilisation of the TTR molecule (to prevent deposition) and dissolution of the amyloid matrix. We describe the latest developments in these approaches to management, many of which are also applicable to wild-type amyloidosis.
authors.affiliation: Department of Cardiology, Hillingdon & Mount Vernon Hospitals NHS Trust, Uxbridge, Middlesex, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Dubrey
authors.affiliation: Isis Pharmaceuticals, Carlsbad, California, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ackermann
authors.affiliation: Division of Medicine, National Amyloidosis Centre, University College London, London, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Gillmore
mesh_terms: D028227:Amyloid Neuropathies, Familial / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001583:Benzoxazoles / Q000627:therapeutic use*; D004318:Doxycycline / Q000627:therapeutic use*; D004452:Echocardiography; D006801:Humans; D016031:Liver Transplantation / Q000379:methods*; D058990:Molecular Targeted Therapy / Q000639:trends*; D011228:Prealbumin / Q000378:metabolism; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D013655:Taurochenodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D001583:Benzoxazoles; D011228:Prealbumin; D034741:RNA, Small Interfering; D013655:Taurochenodeoxycholic Acid; C031655:ursodoxicoltaurine; C547076:tafamidis; D004318:Doxycycline
keywords: GENETICS; TRANSPLANT MEDICINE