A5102022156- Amyloidosis: Diagnosis, Treatment, Outcomes
- Parathyroid Disorders and Treatments
- Cellular transport and secretion
- Alzheimer's disease research and treatments
- Dermatological and Skeletal Disorders
- Protein Kinase Regulation and GTPase Signaling
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Sarcoidosis and Beryllium Toxicity Research
- Peptidase Inhibition and Analysis
- Eosinophilic Disorders and Syndromes
- Neuroendocrine Tumor Research Advances
- Ion channel regulation and function
- Skin and Cellular Biology Research
- Muscle Physiology and Disorders
- Endoplasmic Reticulum Stress and Disease
- Pancreatitis Pathology and Treatment
- IgG4-Related and Inflammatory Diseases
- Pneumocystis jirovecii pneumonia detection and treatment
- Trace Elements in Health
- Genetic Neurodegenerative Diseases
- RNA regulation and disease
- Peripheral Neuropathies and Disorders
- Mitochondrial Function and Pathology
- Bone health and treatments
- RNA Research and Splicing
Hospital de Santo António
2016-2025
Princess Margaret Hospital for Children
2024
Perth Children's Hospital
2024
Centro Hospitalar do Porto
2014-2023
Universidade do Porto
2017-2023
Polytechnic Institute of Portalegre
2022-2023
ERN GUARD-Heart
2023
Amyloidosis Foundation
2023
Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán
2022
Centro Hospitalar de Entre o Douro e Vouga E.P.E.
2021
Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.
Hereditary transthyretin amyloidosis is caused by pathogenic single-nucleotide variants in the gene encoding (TTR) that induce misfolding and systemic deposition of amyloid. Progressive amyloid accumulation leads to multiorgan dysfunction death. Inotersen, a 2′-O-methoxyethyl–modified antisense oligonucleotide, inhibits hepatic production transthyretin.
Transthyretin amyloidosis is caused by the deposition of hepatocyte-derived transthyretin amyloid in peripheral nerves and heart. A therapeutic approach mediated RNA interference (RNAi) could reduce production transthyretin.
To evaluate the efficacy and safety of 18 months tafamidis treatment in patients with early-stage V30M transthyretin familial amyloid polyneuropathy (TTR-FAP).In this randomized, double-blind trial, received 20 mg QD or placebo. Coprimary endpoints were Neuropathy Impairment Score-Lower Limbs (NIS-LL) responder analysis (<2-point worsening) treatment-group difference mean change from baseline Norfolk Quality Life-Diabetic total score (TQOL) intent-to-treat (ITT) population (n = 125). These...
Tafamidis, a transthyretin (TTR) kinetic stabilizer, delayed neuropathic progression in patients with Val30Met TTR familial amyloid polyneuropathy (TTR-FAP) an 18-month randomized controlled trial (study Fx-005). This 12-month, open-label extension study evaluated the long-term safety, tolerability, and efficacy of tafamidis 20 mg once daily 86 who earlier received blinded treatment or placebo. Efficacy measures included Neuropathy Impairment Score Lower Limbs (NIS-LL), Norfolk Quality...
Transthyretin-mediated amyloidosis is an inherited, progressively debilitating disease caused by mutations in the transthyretin gene. This study evaluated safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses patisiran (ALN-TTR02), a small interfering RNA encapsulated within lipid nanoparticles, patients with transthyretin-mediated familial amyloid polyneuropathy (FAP). In this phase II study, FAP were administered 2 intravenous infusions at one following doses: 0.01...
Transthyretin (TTR) amyloidosis is a rare, life-threatening, systemic, autosomal dominant condition occurring in adults, with two main forms: hereditary (associated TTR gene mutations) and wild-type. Studies indicate considerable heterogeneity disease presentation, predominantly polyneuropathic, cardiac, or mixed phenotypes.THAOS - the Amyloidosis Outcomes Survey first global, multicenter, longitudinal, observational survey that collects data on natural history of (ClinicalTrials.gov:...
The study objective was to assess the effect of vutrisiran, an RNA interference therapeutic that reduces transthyretin (TTR) production, in patients with hereditary (ATTRv) amyloidosis polyneuropathy.HELIOS-A a phase 3, global, open-label comparing efficacy and safety vutrisiran external placebo group (APOLLO study). Patients were randomized 3:1 subcutaneous 25 mg every 3 months (Q3M) or intravenous patisiran 0.3 mg/kg weeks (Q3W) for 18 months.HELIOS-A enrolled 164 (vutrisiran, n = 122;...
The recent approval of three drugs for the treatment amyloid transthyretin (ATTR) amyloidosis, both hereditary and wild-type, has opened a new era in care these diseases. ATTR amyloidosis is embedded its pathophysiology, target critical steps cascade. In addition to liver transplant, which removes pathogenic variants, introduction gene silencers allowed suppression wild type mutant (TTR), thus extending potential therapeutic range wild-type cardiac amyloidosis. kinetic stabilisation TTR...
Importance Transthyretin gene silencing is an emerging treatment strategy for hereditary transthyretin (ATTRv) amyloidosis. Objective To evaluate eplontersen, investigational ligand-conjugated antisense oligonucleotide, in ATTRv polyneuropathy. Design, Setting, and Participants NEURO-TTRansform was open-label, single-group, phase 3 trial conducted at 40 sites across 15 countries (December 2019-April 2023) 168 adults with Coutinho stage 1 or 2 polyneuropathy, Neuropathy Impairment Score...
Abstract Familial amyloidotic polyneuropathy (FAP‐type I) was first described in Portugal by Andrade 1952, a time when 54 among 64 patients (belonging to 25 families) originated from Póvoa do Varzim or its surrounding districts. Since then, total of 1,233 patients, belonging 489 pedigrees (so far unrelated), have been diagnosed at Centro de Estudos Paramiloidose, Porto, Portugal. Although age‐of‐onset showed wide range (17 78 years), 87% these developed symptoms before 40 years age (mean...
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. Here we describe rationale design Phase 3 APOLLO study, randomized, double-blind, placebo-controlled, global study to evaluate efficacy safety patisiran patients hATTR amyloidosis polyneuropathy. Eligible are 18–85 years old investigator-estimated survival ≥2 years,...
Transthyretin amyloidosis (ATTR amyloidosis) is a heterogeneous disorder with cardiac, neurologic, and mixed phenotypes. We describe the phenotypic genotypic profiles of this disease in continental Western Europe as it appears from Amyloidosis Survey (THAOS).THAOS an ongoing, worldwide, longitudinal, observational survey established to study differences presentation, diagnosis, natural history ATTR subjects. At data cut-off, 1411 symptomatic subjects nine European countries were enrolled...
To assess the association between severity of neuropathy and disease stage, estimate rate progression in a retrospective cross-sectional analysis multinational population patients with familial amyloidotic polyneuropathy (FAP).We characterize available FAP France, United States, Portugal, Italy. Neuropathy Impairment Scores (NIS), time from symptom onset to NIS measurement, disability (PND) scores, manual grip strength data were collected. We estimated using Loess Fit Gompertz models.For 283...
Abstract Background Transthyretin amyloidosis (also known as ATTR amyloidosis) is a systemic, life-threatening disease characterized by transthyretin (TTR) fibril deposition in organs and tissue. A definitive diagnosis of often challenge, large part because its heterogeneous presentation. Although was previously considered untreatable, disease-modifying therapies for the treatment this have recently become available. This article aims to raise awareness initial symptoms among general...