The transthyretin amyloidoses: advances in therapy.
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.
['Dubrey|Simon|S|', 'Ackermann|Elizabeth|E|', 'Gillmore|Julian|J|']
D028227:Amyloid Neuropathies, Familial D000894:Anti-Inflammatory Agents, Non-Steroidal D001583:Benzoxazoles D004318:Doxycycline D004452:Echocardiography D006801:Humans D016031:Liver Transplantation D058990:Molecular Targeted Therapy D011228:Prealbumin D011379:Prognosis D034741:RNA, Small Interfering D013655:Taurochenodeoxycholic Acid
GENETICS TRANSPLANT MEDICINE