2016 Volume 33 Issue 2 Pages 163-166
Hereditary ATTR amyloidosis is an autosomal dominant genetic disorder with systemic deposition of amyloid fibrils induced by transthyretin (TTR) gene mutation. Clinically, this disorder is characterized by progressive nerve length–dependent sensorimotor and autonomic neuropathy, as well as non–neuropathic manifestations of cardiomyopathy, gastroenteropathy, ocular amyloidosis, and leptomeningeal amyloidosis/cerebral amyloid angiopathy. To date, more than 100 TTR gene mutations have been reported, the most common of which is V30M (p.V50M) that is found worldwide. Orthotopic liver transplantation, which replaces the variant TTR gene with the wild–type gene in the liver, the main source of serum circulating TTR was shown to be able to halt or slow neurological progression, and is at present the standard–of–care treatment in patients aged ＜50 with V30M mutation. However, large numbers of patients are not suitable transplant candidates. Recently, the clinical effects of TTR tetramer stabilisers, diflunisal and tafamidis, were demonstrated in randomised clinical trials, and tafamidis has been approved for treatment of hereditary ATTR amyloidosis in several European countries, Japan, Argentina, and Mexico. Moreover, small interfering RNAs and antisense oligonucleotides for suppression of TTR synthesis are promising therapeutic approaches to ameliorate hereditary ATTR amyloidosis and are currently in phase III clinical trials. However, these disease–modifying therapies cannot prevent the progression of ocular amyloidosis and leptomeningeal amyloidosis/cerebral amyloid angiopathy, due to variant TTR synthesis by the retinal pigment epithelium and choroid plexus. New therapeutic strategies should be developed to ameliorate ATTR ocular amyloidosis and leptomeningeal amyloidosis/cerebral amyloid angiopathy.