10 documents found, page 1 of 1
An Antisense Oligonucletide based therapy for a rare disease: in vitro and in v...
Gonçalves, M.; Matos, L.; Santos, J.I.; Coutinho, M.F.; Prata, M.J.; Pires, M.J.; Oliveira, P.A.; Alves, SandraMucolipidosis type II (ML II) is a Lysosomal Storage Disorder caused by the deficiency of the enzyme GlcNAc-1-phosphotransferase. This enzyme is responsible for the addition of the mannose-6-phosphate marker to lysosomal enzymes allowing their targeting to lysosomes. From the several ML II mutations, the deletion of two nucleotides from GNPTAB exon 19 (c.3503_3504del) is the most frequent, making it a good targ...
The disease modelling value of a folklore FAIRYtale: SHEDing light over a speci...
Carvalho, S.; Santos, J.I.; Moreira, L.; Gaspar, P.; Gonçalves, M.; Encarnação, M.; Ribeiro, D.; Duarte, A.; Prata, M.J.; Coutinho, M.F.The problem we are addressing: Despite extensive research, the links between accumulation of glycosaminoglycans (GAGs) and the clinical features seen in patients suffering from various forms of Mucopolysaccharidoses (MPSs) have yet to be further elucidated. These Lysosomal Storage Diseases (LSDs) present symptoms, which may (or may not) include critical musculoskeletal and cardiovascular alterations, respirator...
Development of RNA based approaches to exploit alternative therapies for Lysoso...
Matos, L.; Santos, J.I.; Rocha, M.; Coutinho, M.F.; Gaspar, P.; Voltolini Velho, R.; Braulke, T.; Prata, M.J.; Alves, S.Treatment strategies such enzyme-replacement therapy and substrate reduction, among others, are available for some Lysosomal Storage Diseases, yet still with some limitations. In recent years, the RNA molecule became one of the most promising targets for therapeutic intervention and currently, a large number of RNA-based therapies are being investigated at the basic research level and in late-stage clinical tri...
The use of a modified U1 snRNA as a therapeutic strategy to correct a 5’ splice...
Matos, L.; Santos, J.I.; Rocha, M.; Coutinho, M.F.; Prata, M.J.; Alves, S.Genetic therapy directed towards the correction of RNA missplicing is being investigated not only at basic research level but even in late-stage clinical trials. Many mutations that change the normal splicing pattern and lead to aberrant mRNA production have been identified in Lysosomal Storage Disorders (LSDs). The Mucopolysaccharidosis IIIC (MPS IIIC) is a LSD caused by mutations in the HGSNAT gene, encoding ...
The use of a modified U1 snRNA as a therapeutic strategy to correct a 5’ splice...
Santos, J.I.; Matos, L.; Rocha, M.; Coutinho, M.F.; Prata, M.J.; Alves, S.Genetic therapy directed towards the correction of RNA missplicing is being investigated not only at basic research level but even in late-stage clinical trials. Many mutations that change the normal splicing pattern and lead to aberrant mRNA production have been identified in Lysosomal Storage Disorders (LSDs). The Mucopolysaccharidosis IIIC (MPS IIIC) is a LSD caused by mutations in the HGSNAT gene, encoding ...
Mucopolysaccharidoses type III: toward a siRNA-containing nanoparticle targeted...
Coutinho, M.F.; Santos, J.I.; Gaspar, P.; Alves, S.The classical therapeutic approach for LSD, enzyme replacement therapy, would hardly rise as a potentially successful tool to reduce the disease burden in MPS III patients, as it is long known to have no impact on neuropathology. A tempting alternative, however, would be to block substrate accumulation upstream, by decreasing its synthesis. That concept is known as substrate reduction therapy (SRT). Having this...
Environmental benchmarks based on ecotoxicological assessment with planktonic s...
Vidal, T.; Santos, J.I.; Queirós, L.; Ré, A.; Abrantes, N.; Gonçalves, F. J. M.; Pereira, J. L.Freshwater ecosystems face widespread diffuse and point-source contamination. Species Sensitivity Distributions (SSDs) have been used as a tool to determine chemical concentration benchmarks that represent protective levels for most species in the environment. Here we used a SSD approach to assess on the adequacy of standard planktonic organisms to reflect the response of benthic communities, critically support...
Less is More: Substrate Reduction Therapy for Lysosomal Storage Disorders
Coutinho, Maria Francisca; Santos, J.I.; Alves, SandraThe concept of enzyme replacement as a potential therapeutic approach to ameliorate lysosomal storage disorders (LSDs) is virtually as old as the concept of LSD itself. In fact, both concepts were established right after the first enzymatic deficiency underlying an LSD was described, and enzyme replacement therapy (ERT) remained the golden standard for LSD treatment for years. Nevertheless, its ineffectiveness ...
Genetically Modulated Substrate Reduction Therapy for Sanfilippo syndrome – pro...
Santos, J.I.; Coutinho, Maria Francisca; Gaspar, P.; Alves, S.Introduction: Mucopolysaccharidosis type III (MPS III) refers to a group of five autosomal recessive neurodegenerative lysosomal storage disorders caused by the incomplete lysosomal degradation of the heparan sulphate (HS) that accumulates in patient cells and triggers disease. The main characteristic of this disease is the degeneration of the central nervous system, resulting in mental retardation and hyperact...
Molecular Characterization of a Novel Mucopolysaccharidosis (MPS) type VI-causi...
Coutinho, Maria Francisca; Encarnação, M.; Santos, J.I.; Alves, S.Introduction: With its unprecedented throughput, scalability and speed, next-generation sequencing (NGS) is revolutionizing clinical research. Targeted sequencing in particular is now available in many labs. Still, whenever a novel variant is detected, its pathogenicity must be carefully assessed and every now and again, a case pops up to highlight how tricky and delicate this process can be. Here we present a ...