Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a progressive, fatal, inherited disorder first identified in Portugal and now recognized in all continents. Over the past decade, thanks to the availability of the genetic test, our knowledge on the range of clinical expressions of this disorder has expanded, including different patterns and progression rates of the neuropathy, as well as aspects of the cardiomyopathy, which can be prominent. In the mean time, new tools are being developed to detect earlier TTR amyloid deposition such as cardiac scintigraphy with technetium-labelled pyrophosphate tracers or small nerve fiber alterations from skin biopsies, or using neurophysiological approaches as well as magnetic resonance neurography (MRN). Such refinements, along with an increased awareness of the disease, should reduce the diagnostic delay and facilitate early treatment. In this regard, thanks to a better understanding of the TTR amyloid formation, major advances have been made, allowing for therapeutic developments which are less invasive than liver transplantation (LT). TTR stabilizer drugs are safe and seem to delay the disease progression in some groups of patients. Indeed, positive results have just been released from 2 phase III trials on TTR gene modifiers, namely silencing RNA and antisense oligonucleotide therapies. These recent advances open a new area in the field with the hope that we can safely bring about long-term stabilization of the disease. Furthermore, immunotherapies targeting the amyloid deposits are being explored.
Keywords: Gene modifyers therapy; Genetic; Neuropathy; Transthyretin amyloidosis; Treatment.