25 documents found, page 1 of 3
Early data on long‐term efficacy and safety of inotersen in patients with hered...
Brannagan, T. H.; Wang, A. K.; Coelho, T.; Waddington Cruz, M.; Polydefkis, M. J.; Dyck, P. J.; Plante‐Bordeneuve, V.; Berk, J. L.; Barroso, F.Background and purpose: Hereditary transthyretin (hATTR) amyloidosis causes progressive polyneuropathy resulting from transthyretin (TTR) amyloid deposition throughout the body, including the peripheral nerves. The efficacy and safety of inotersen, an antisense oligonucleotide inhibitor of TTR protein production, were demonstrated in the pivotal NEURO-TTR study in patients with hATTR polyneuropathy. Here, the l...
A pair of peptides inhibits seeding of the hormone transporter transthyretin in...
Saelices, L.; Nguyen, B.; Chung, K.; Wang, Y.; Ortega, A.; Lee, J.; Coelho, T.; Bijzet, J.; Benson, M.; Eisenberg, D.The tetrameric protein transthyretin is a transporter of retinol and thyroxine in blood, cerebrospinal fluid, and the eye, and is secreted by the liver, choroid plexus, and retinal epithelium, respectively. Systemic amyloid deposition of aggregated transthyretin causes hereditary and sporadic amyloidoses. A common treatment of patients with hereditary transthyretin amyloidosis is liver transplantation. However,...
Advances in the treatment of hereditary transthyretin amyloidosis: A review
Gertz, M.; Mauermann, M.; Grogan, M.; Coelho, T.Introduction: Amyloid transthyretin amyloidosis (ATTR) is a progressive and often fatal disease caused by the buildup of mutated (hereditary ATTR [hATTR]; also known as ATTR variant [ATTRv]) or normal transthyretin (wild-type ATTR) throughout the body. Two new therapies-inotersen, an antisense oligonucleotide therapy, and patisiran, an RNA interference therapy-received marketing authorization and represent a si...
Predictive model of response to tafamidis in hereditary ATTR polyneuropathy
Monteiro, C.; Mesgazardeh, J.; Anselmo, J.; Fernandes, J.; Novais, M.; Rodrigues, C.; Brighty, G.; Powers, D.; Powers, E.; Coelho, T.; Kelly, J.BACKGROUNDThe hereditary transthyretin (TTR) amyloidoses are a group of diseases for which several disease-modifying treatments are now available. Long-term effectiveness of these therapies is not yet fully known. Moreover, the existence of alternative therapies has resulted in an urgent need to identify patient characteristics that predict response to each therapy.METHODSWe carried out a retrospective cohort s...
Natural history and survival in stage 1 Val30Met transthyretin familial amyloid...
Coelho, T.; Inês, M.; Conceição, I.; Soares, M.; de Carvalho, M.; Costa, J.Objective: To assess the natural history and treatment effect on survival among patients with transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) stage 1 Val30Met. Methods: Multi-institutional, hospital-based study of patients with TTR-FAP Val30Met prospectively followed up until December 2016, grouped into untreated (n = 1,771), liver transplant (LTx)-treated (n = 957), or tafamidis-treated (n =...
Corino de Andrade disease: mechanisms and impact on reproduction
Lopes, R.; Coelho, T.; Barros, A.; Sousa, M.Familial amyloid polyneuropathy was first described by Corino de Andrade in 1952 in Northern Portugal. It is a fatal autosomal dominant neurodegenerative disorder characterized by a progression of neurologic symptoms, beginning early in the reproductive life. The Transthyretin gene mutation originates a mutated protein that precipitates in the connective tissue as amyloid deposits. This disease is presently nam...
Trial design and rationale for APOLLO, a Phase 3, placebo-controlled study of p...
Adams, D.; Suhr, O.; Dyck, P.; Litchy, W.; Leahy, R.; Chen, J.; Gollob, J.; Coelho, T.Background Patisiran is an investigational RNA interference (RNAi) therapeutic in development for the treatment of hereditary ATTR (hATTR) amyloidosis, a progressive disease associated with significant disability, morbidity, and mortality. Methods Here we describe the rationale and design of the Phase 3 APOLLO study, a randomized, double-blind, placebo-controlled, global study to evaluate the efficacy and safet...
Exonization of an Intronic LINE-1 Element Causing Becker Muscular Dystrophy as ...
Gonçalves, A.; Oliveira, J.; Coelho, T.; Taipa, R.; Melo-Pires, M.; Sousa, M.; Santos, R.A broad mutational spectrum in the dystrophin (DMD) gene, from large deletions/duplications to point mutations, causes Duchenne/Becker muscular dystrophy (D/BMD). Comprehensive genotyping is particularly relevant considering the mutation-centered therapies for dystrophinopathies. We report the genetic characterization of a patient with disease onset at age 13 years, elevated creatine kinase levels and reduced d...
Familial amyloid polyneuropathy in Portugal: New genes modulating age-at-onset
Santos, D.; Coelho, T.; Alves-Ferreira, M.; Sequeiros, J.; Mendonça, D.; Alonso, I.; Lemos, C.; Sousa, A.OBJECTIVES: Familial amyloid polyneuropathy (FAP ATTRV30M) shows a wide variation in age-at-onset (AO) between clusters, families, and among generations. We will now explore some candidate genes involved in altered disease pathways in order to assess their role as genetic modifiers of AO, using a family-centered approach. METHODS: We analyzed 62 tagging SNPs from nine genes-NGAL,MMP-9,BGN,MEK1,MEK2,ERK1,ERK2,HS...
Mechanism of Action and Clinical Application of Tafamidis in Hereditary Transth...
Coelho, T.; Merlini, G.; Bulawa, C.; Fleming, J.; Judge, D.; Kelly, J.; Maurer, M.; Planté-Bordeneuve, V.; Labaudinière, R.; Mundayat, R.; Riley, S.Transthyretin (TTR) transports the retinol-binding protein-vitamin A complex and is a minor transporter of thyroxine in blood. Its tetrameric structure undergoes rate-limiting dissociation and monomer misfolding, enabling TTR to aggregate or to become amyloidogenic. Mutations in the TTR gene generally destabilize the tetramer and/or accelerate tetramer dissociation, promoting amyloidogenesis. TTR-related amyloi...