What's new in the treatment of amyloidosis? Part 3: familial amyloidotic polyneuropathy

Abstract

Transthyretin amyloidosis is a rare disease caused by the deposition of fibrils of this protein in various tissues, with cardiac and neurological involvement being the most common. It can be acquired (formerly known as 'senile amyloidosis') or hereditary due to mutations in the gene encoding transthyretin (TTR), although this is less common. A common manifestation of mutated TTR (hereafter referred to as ATTRv) is familial amyloid polyneuropathy.

At the Hospital Italiano de Buenos Aires, since 2010, there has been a transdisciplinary group of professionals united by the interest in optimizing the care of people with amyloidosis. This group is formed by professionals from different specialties, with a national reference, focusing on care, education, and research. In 2020, this team, known as the Amyloidosis Study Group (GEA), developed clinical practice guidelines for treating familial amyloid polyneuropathy.

Since then, numerous clinical trials have been published that strengthen the available knowledge and new lines of research are being developed, enhancing and encouraging study in this area. This review provides an update of the existing guidelines regarding transthyretin familial amyloid polyneuropathy and explores the state of the art.

In the treatment of familial amyloid polyneuropathy, the use of patisiran (a small interfering RNA or siRNA aimed at interfering with the hepatic synthesis of transthyretin) is well known. It is currently also approved for patients with a previous liver transplant and symptomatic progression. In addition to this medication, vutrisiran is currently recommended, from the same pharmacological family, but with an easier dosing regimen and an acceptable side effect profile.

In vivo gene editing is also in vogue as a new line of research, being part of multiple ongoing clinical trials.