[Familial amyloid polyneuropathies: therapeutic issues]

Patients with familial amyloidpolyneuropathies (FAP) require multidisciplinary neurologic and cardiologic management, including specific treatments to control the progression of systemic amyloidogenesis, symptomatic treatment of peripheral and autonomic neuropathies, and management of severe organ involvement (heart, eyes, kidneys). The first-line specific treatment of choice for met30 TTR-FAP is liver transplantation (LT) which suppresses the main source of mutant TTR, halts the progression of neuropathy in 70% of cases, and doubles the median survival time. Dual kidney-liver or heart-liver transplantation may be appropriate for patients with severe renal or cardiac failure. Tafamidis (Vyndaqel(R), Pfizer), a novel stabilizer of tetrameric TTR, has shown short-term effectiveness in slowing the progression of peripheral neuropathy in very early stages of met30 TTR-FAP This drug should thus be proposed for stage 1 symptomatic polyneuropathy. Other innovative medicines (RNA interference, antisense oligonucleotides) have been developed to block hepatic production of both mutant and wildtype TTR (noxious in late-onset forms of NAH after age 50 years), and to remove amyloid deposits (monoclonal anti-SAP). Clinical trials should first include patients with late-onset FAP or non-met30 TTR-FAP who are less responsive to LT7 and patients in whom Vyndaqel(R) is ineffective or inappropriate. Initial and periodic cardiac assessment is necessary, as cardiac impairment is inevitable and largely responsible for mortality. Symptomatic treatment is crucial to improve these patients' quality of life. Familial screening for carriers of the TTR gene mutation and regular clinical examination are essential to detect disease onset and to start specific therapy in a timely manner.