Treatment of familial amyloid polyneuropathy

The treatment of familial amyloid polyneuropathies (FAP) is complex and requires a neurological and cardiological multi-disciplinary coverage. It includes specific treatments to control the progression of the systemic amyloidogenesis, the symptomatic treatment of the peripheral and autonomic neuropathy (digestive, urinary, sexual, postural hypotension) and the treatment of organs severely involved by amyloidosis (heart, eyes, kidneys). First line specific treatment of met30 TTR-FAP is liver transplantation (LT) which allows to suppress the main source of mutant TTR, to stop the progression of the neuropathy in 70 % of cases at long-term (with an experience of 18 years) and to double the median survival. In case of severe renal or cardiac insufficiency, a double transplant kidney liver or heart liver con be discussed. The tafamidis (in temporary authorization of use in France) is a stabilizing medicine of the tetrameric TTR which showed in very early stages of met30 TTR-FAP short-term capacities to stop the progress of the peripheral neuropathy in 60 % of the cases versus 38 % with placebo. It should be proposed in case of contraindication of TH (age > 70 years [20 % of the cases]), of very early stages (very low NIS-LL score), or for the period of wait of LT. Other innovative medicines issued from biopharmaceutical companies have been developed to block the hepatic production of both mutant and wild TTR which are noxious in the late forms NAH (>50 years old) (RNAi [RNA interference] therapeutics, AntiSens oligonucleotids), for removing the amyloid deposits (monoclonal antibody anti-SAP), or to slow down the formation of deposits of TTR and amyloidosis (combination of doxycycline-TUDCA). Clinical trials should be first addressed to the patients with a late onset of FAP or non-met30 TTR-FAP who are less responding to LT and patients with contraindications in the LT. Initial cardiac assessment and periodic cardiac investigations are important for the FAP according to the frequency of cardiac impairment which is responsible of high rote of mortality. Conduction disorders (atrio-ventricular blocks) require the implantation of a pacemaker in about one third of the cases during the evolution of the disease. A myocardial infiltration is detected in two third of the cases and is for a long time latent; it remains often limited to a diastolic dysfunction which can be responsible for hemodynamical difficulties during the LT; it evolves sometimes, late, towards a systolic dysfunction of bad prognosis. A combined liver heart transplantation is proposed in cases of severe cardiac involvement which ore contraindication to the LT only, essentially in forms not met30. In every case of FAP, a regular cardiological follow-up is required for life, because of the progress of the cardiac involvement, which is not always stopped by the liver transplantation. The symptomatic treatments are indispensable to improve the quality of life of the patients: neurogenic pains, urinary disorders, liqueurs, sexual impotence, postural hypotension. The familial screening of the carriers of the TTR gene mutation and their regular follow-up by appropriate clinical examination and complementary investigations are major to detect early the onset of the disease to start as soon as possible specific therapy.