A5070564223- Esophageal Cancer Research and Treatment
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Gastric Cancer Management and Outcomes
- Esophageal and GI Pathology
- Alzheimer's disease research and treatments
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Lung Cancer Diagnosis and Treatment
- Dementia and Cognitive Impairment Research
- Cellular transport and secretion
- Protein Kinase Regulation and GTPase Signaling
- Cancer, Lipids, and Metabolism
- Gastrointestinal Tumor Research and Treatment
- Cholinesterase and Neurodegenerative Diseases
- Medical Imaging Techniques and Applications
- Advanced Fluorescence Microscopy Techniques
- Moyamoya disease diagnosis and treatment
- Parathyroid Disorders and Treatments
- Tryptophan and brain disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Tracheal and airway disorders
- Head and Neck Cancer Studies
- Parkinson's Disease Mechanisms and Treatments
- Endoplasmic Reticulum Stress and Disease
- Neurological Complications and Syndromes
- Prostate Cancer Treatment and Research
Hospital Curry Cabral
2024
IPO Porto
2020-2024
Scripps Research Institute
2015-2022
Ionis Pharmaceuticals (United States)
2019-2021
Clinics Hospital of Ribeirão Preto
2020
Universidade de São Paulo
2020
Instituto Português de Oncologia Francisco Gentil
2020
University of Montana
2018
Centro Hospitalar do Porto
2012-2015
Hospital de Santo António
2012-2015
Accumulation of tau pathology in Alzheimer disease (AD) correlates with cognitive decline. Anti-tau immunotherapies were proposed as potential interventions AD. While antibodies targeting N-terminal failed to demonstrate clinical efficacy prodromal-to-mild AD, their utility at other stages was not evaluated prior studies. Lauriet is a phase 2 study an anti-tau monoclonal antibody, semorinemab, patients mild-to-moderate
The transthyretin (TTR) amyloidoses are a group of degenerative diseases caused by TTR aggregation, requiring rate-limiting tetramer dissociation. Kinetic stabilization TTR, preferential binding drug to the native over dissociative transition state, dramatically slows progression familial amyloid polyneuropathy. An established method for quantifying kinetic stability recombinant tetramers in buffer is subunit exchange, which tagged homotetramers added untagged at equal concentrations measure...
BACKGROUND. The hereditary transthyretin (TTR) amyloidoses are a group of diseases for which several disease-modifying treatments now available. Long-term effectiveness these therapies is not yet fully known. Moreover, the existence alternative has resulted in an urgent need to identify patient characteristics that predict response each therapy.
Increasing evidence supports the hypothesis that soluble misfolded protein assemblies contribute to degeneration of postmitotic tissue in amyloid diseases. However, there is a dearth reliable nonantibody-based probes for selectively detecting oligomeric aggregate structures circulating plasma or deposited tissues, making it difficult scrutinize this patients. Hence, understanding structure-proteotoxicity relationships driving diseases remains challenging, hampering development early...
AKCEA-TTR-LRx is a ligand-conjugated antisense (LICA) drug in development for the treatment of hereditary transthyretin amyloidosis (hATTR), fatal disease caused by mutations (TTR) gene. shares same nucleotide sequence as inotersen, an medicine approved use hATTR polyneuropathy (hATTR-PN). Unlike conjugated to triantennary N-acetylgalactosamine moiety that supports receptor-mediated uptake hepatocytes, primary source circulating TTR. This advanced design increases potency allow lower and...
Hereditary transthyretin (TTR) amyloidosis associated with the TTRV30M (p.TTRV50M) mutation presents predominantly as an axonal polyneuropathy, variable involvement of other organs. Serious central nervous system (CNS) and eye manifestations, including stroke, dementia, vitreous opacities glaucoma, have been reported in untreated V30M TTR patients, these patients after treatment liver transplantation (LT). Distinct therapies for developed during last decade exhibit promising results slowing...
Significance Treating the transthyretin (TTR) amyloidoses early maximizes clinical response. Soluble nonnative protein oligomers are cytotoxic in cultured cell lines, primary cells, and animal models. Here we report an immunoassay for quantifying nonnative, oligomeric TTR (NNTTR) levels human V30M polyneuropathy plasma ( n = 81). High NNTTR pretreatment significant predicting which patients less likely to respond tafamidis P 0.0025). The extent of decrease does not differ between responders...
Abstract Targeting of tau pathology has long been proposed as a potential therapeutic strategy for Alzheimer’s disease (AD). Semorinemab is humanized IgG4 monoclonal antibody that binds to all known isoforms full-length with high affinity and specificity. Semorinemab’s safety efficacy have studied in two Phase 2 randomized, double-blind, placebo-controlled, parallel-group clinical trials: Tauriel (prodromal-to-mild AD; NCT03289143 ) Lauriet (mild-to-moderate NCT03828747 ). CSF was collected...
Abstract INTRODUCTION Growing evidence suggests a role for neuroinflammation in Alzheimer's disease (AD). We investigated complement pathway activity AD patient cerebrospinal fluid (CSF) and evaluated its modulation by the anti‐tau antibody semorinemab. METHODS Immunoassays were applied to measure CSF proteins C4, factor B (FB), C3 their cleavage fragments C4a, C3a, Bb (Bb) patients separate cognitively unimpaired (CU) cohort. RESULTS All measured increased versus CU subjects, with C4a...
ABSTRACT INTRODUCTION Growing evidence suggests a role for neuroinflammation in Alzheimer’s Disease (AD) pathogenesis. We investigated the complement system, component of innate immunity, AD patient cerebrospinal fluid (CSF) and evaluated its modulation by anti-tau antibody semorinemab. METHODS Immunoassays were applied to measure intact (inactive) cleaved (active) CSF proteins C4, Factor B C3 patients separate cognitively normal (CN) cohort. RESULTS All measured increased vs CN subjects,...
ABSTRACT INTRODUCTION Semorinemab, an anti-tau monoclonal antibody, was evaluated in two Phase II trials as a disease-modifying treatment for Alzheimer’s disease (AD). Plasma and cerebrospinal fluid (CSF) samples were collected from trial participants to evaluate the pharmacodynamic effects of semorinemab elucidate its mechanism action. METHODS Qualified immunoassays used measure plasma CSF biomarkers tau, amyloidosis, glial activity, neuroinflammation, synaptic function, neurodegeneration...
Semorinemab, an anti-tau monoclonal antibody, was assessed in two Phase II trials for Alzheimer's disease (AD). Plasma and cerebrospinal fluid (CSF) biomarkers provided insights into the drug's potential mechanism of action.
Excited-state intramolecular proton transfer involves a photochemical isomerization and creates the opportunity for emission of two distinct wavelengths light from single fluorophore. The selectivity between these is dependent on environment around fluorophore suggests possibility ratiometric monitoring protein microenvironments. Unfortunately, nonspecific binding ESIPT fluorophores does not often lead to dramatic changes in ratio emission. A pocket was designed selectively discriminate...
TTR aggregation causes hereditary transthyretin (TTR) polyneuropathy (ATTRv-PN) in individuals with destabilised variants. ATTRv-PN can be treated ligands that bind and prevent aggregation. One such ligand, tafamidis, is widely approved to treat ATTRv-PN. We explore how stabilisation markers relate clinical efficacy 210 patients taking tafamidis. concentration patient plasma was measured before after tafamidis treatment using assays for native or combined + non-native TTR. tetramer...
Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be present negative family history and, especially in younger patients, normal brain magnetic resonance. For this reason, those CADASIL patients that only migraine may misdiagnosed. In the case of motor aura, sporadic hemiplegic (SHM) is one possible misdiagnoses. Case results: We a patient who, first years her disease, met clinical criteria for SHM. A diagnosis was considered...
Objective: This study aims to determine if AKCEA-TTR-LRx, an antisense oligonucleotide (ASO), is effective and safe as compared historical placebo, for the treatment of hereditary transthyretin-mediated amyloid polyneuropathy (hATTR-PN). Background: hATTR-PN a progressive fatal axonal sensorimotor autonomic neuropathy caused by misfolding/aggregation transthyretin (TTR), liver produced protein. Inotersen (Tegsedi™) ASO approved treat that acts reducing TTR production. Design/Methods:...