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...
SCARB2 mutations as modifiers in Gaucher disease: the wrong enzyme at the wrong...
Coutinho, M.F.; Lacerda, L.; Gaspar, A.; Pinto, E.; Ribeiro, I.; Laranjeira, F.; Ribeiro, H.; Silva, E.; Ferreira, C.; Prata, M.J.; Alves, S.Unlike most lysosomal proteins, β-glucocerebrosidase (GCase), the hydrolase defective in Gaucher disease (GD), is delivered to lysosomes through its interaction with the transmembrane protein LIMP2. A few years ago, mutations in its coding gene, SCARB2, were reported to modify the severity of GD phenotype. The existence of a great variety of GD phenotypes is well-known, with numerous patients who carry identica...
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 ...
SCARB2 mutations as modifiers in Gaucher disease: the wrong enzyme at the wrong...
Coutinho, Maria Francisca; Lacerda, L.; Gaspar, A.; Pinto, E.; Ribeiro, I.; Laranjeira, F.; Ribeiro, H.; Silva, E.; Ferreira, C.; Prata, M.J.; Alves, S.Unlike most lysosomal proteins, β-glucocerebrosidase (GCase), the hydrolase defective in Gaucher disease (GD), is delivered to lysosomes through its interaction with the transmembrane protein LIMP2. A few years ago, mutations in its coding gene, SCARB2, were reported to modify the severity of GD phenotype. The existence of a great variety of GD phenotypes is well-known, with numerous patients who carry identica...
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 ...
Unverricht-Lundborg disease: development of splicing therapeutic approaches for...
Matos, L.; Duarte, A.J.; Ribeiro, D.; Jordan, P.; Prata, M.J.; Chaves, J.; Desviat, L.R.; Pérez, B.; Amaral, O.; Alves, S.Unverricht-Lundborg disease (ULD) is the most common form of progressive myoclonic epilepsy worldwide. It is an autosomal recessive neurodegenerative disorder caused by mutations in the cystatin B gene (CSTB) that encodes an inhibitor of several lysosomal cathepsins. An unstable expansion, missense, nonsense, frameshift and mutations that may lead to alternative splicing have been described as causal of ULD. Re...
Molecular and computational analyses of genes involved in mannose 6-phosphate i...
Coutinho, M.F.; Lacerda, L.; Pinto, E.; Ribeiro, H.; Macedo-Ribeiro, S.; Castro, L.; Prata, M.J.; Alves, S.The newly-synthesized lysosomal enzymes travel to the trans-Golgi network (TGN) and are then driven to the acidic organelle. While the best-known pathway for TGN-to-endosome transport is the delivery of soluble hydrolases by the M6P receptors (MPRs), additional pathways do exist, as showed by the identification of two alternative receptors: LIMP-2, implicated in the delivery of β-glucocerebrosidase; and sortili...
Prenatal skeletal dysplasia phenotype in severe MLII alpha/beta with novel GNPT...
Aggarwal, S.; Coutinho, M.F.; Dalal, A.; Jain, S.J.; Prata, M.J.; Alves, S.We report a neonate who was diagnosed as a case of skeletal dysplasia during pregnancy, and was subsequently diagnosed as a case of MLII alpha/beta on the basis of clinical and radiological findings and molecular testing of the parents. A novel GNPTAB mutation c.1701delC [p.F566LfsX5] was identified in the father. The case reiterates the severe prenatal phenotype of MLII alpha/beta which mimics skeletal dysplasia...