David Adams1, Michel Slama2. 1. Service de Neurologie, CHU Bicetre, Assistance Publique - Hôpitaux de Paris, National Reference Center for Familial Amyloid Polyneuropathy, Le Kremlin Bicêtre, INSERM U1195, Université Paris Saclay. 2. Service de Cardiologie, CHU X. Bichat, Assistance Publique - Hôpitaux de Paris, Centre de Compétence Amylose Cardiaque, Université Paris Saclay, Paris, France.
Abstract
PURPOSE OF REVIEW: Hereditary transthyretin amyloidosis (ATTRv) is a rare autosomal dominant, life-threatening disease. Until recently only early stages of ATTRv-PN (polyneuropathy) had access to disease-modifying therapy (DMT), whereas there was no specific treatment for ATTRv-CM (cardiomyopathy). This review updates our knowledge about results of three phase 3 clinical trials, expert's consensus for early diagnosis and emerging biomarkers. RECENT FINDINGS: Two phase 3 studies using RNAi and antisense oligonucleotides (ASO) were successful. Primary endpoints were progression of neuropathic score mNIS +7 and quality of Life (QOL) in a population of ATTRv-PN at different levels of severity. They knock downed circulating amyloidogenic mutant and wild-type TTR. Safety concerned ASO with a risk of thrombocytopenia. RNAi showed possible reversibility of the disease. Phase 3 ATTRACT trial-tested tafamidis versus placebo in patients with ATTRv-CM and ATTRwt-CM and showed a significant reduction of all-cause mortality and rates of cardiovascular-related hospitalizations. All three drugs obtained marketing authorization by European Medicines Agency (EMA) and Food and drug administration (FDA). Early diagnosis criteria for ATTRv-PN and ATTRv-CM are available. Ongoing clinical trials for ATTRv are presented. New biomarkers are plasma neurofilament light chain, intraepidermal nerve fiber density. SUMMARY: The majority of patients with ATTRv may have now access to a DMT. Criteria for early diagnosis are available.
PURPOSE OF REVIEW: Hereditary transthyretin amyloidosis (ATTRv) is a rare autosomal dominant, life-threatening disease. Until recently only early stages of ATTRv-PN (polyneuropathy) had access to disease-modifying therapy (DMT), whereas there was no specific treatment for ATTRv-CM (cardiomyopathy). This review updates our knowledge about results of three phase 3 clinical trials, expert's consensus for early diagnosis and emerging biomarkers. RECENT FINDINGS: Two phase 3 studies using RNAi and antisense oligonucleotides (ASO) were successful. Primary endpoints were progression of neuropathic score mNIS +7 and quality of Life (QOL) in a population of ATTRv-PN at different levels of severity. They knock downed circulating amyloidogenic mutant and wild-type TTR. Safety concerned ASO with a risk of thrombocytopenia. RNAi showed possible reversibility of the disease. Phase 3 ATTRACT trial-tested tafamidis versus placebo in patients with ATTRv-CM and ATTRwt-CM and showed a significant reduction of all-cause mortality and rates of cardiovascular-related hospitalizations. All three drugs obtained marketing authorization by European Medicines Agency (EMA) and Food and drug administration (FDA). Early diagnosis criteria for ATTRv-PN and ATTRv-CM are available. Ongoing clinical trials for ATTRv are presented. New biomarkers are plasma neurofilament light chain, intraepidermal nerve fiber density. SUMMARY: The majority of patients with ATTRv may have now access to a DMT. Criteria for early diagnosis are available.
Authors: Gita A Pathak; Antonella De Lillo; Frank R Wendt; Flavio De Angelis; Dora Koller; Brenda Cabrera Mendoza; Daniel Jacoby; Edward J Miller; Joel N Buxbaum; Renato Polimanti Journal: Amyloid Date: 2021-12-22 Impact factor: 6.571
Authors: Jaleh S Mesgarzadeh; Isabelle C Romine; Ethan M Smith-Cohen; Julia M D Grandjean; Jeffery W Kelly; Joseph C Genereux; R Luke Wiseman Journal: Cells Date: 2022-05-17 Impact factor: 7.666