37 documents found, page 1 of 4

Can an Antisense Oligonucleotide Exon Skipping Rewrite the Story of N-Acetylglu...

Mucolipidosis II (ML II) is a Lysosomal Storage Disorder caused by N-acetylglucosamine-1-phosphotransferase (GlcNAc-PT) deficiency, which impairs the trafficking of lysosomal hydrolases. Of all ML II mutations, c.3503_3504delTC in GNPTAB exon 19 is the most frequent, making it a good target for a personalized therapy. Here, we explored an innovative therapeutic strategy based on the use of antisense oligonucleo...

An engineered U1 snRNA-based therapeutic approach can efficiently rescue a 5’ s...

A significant number of splicing mutations have been identified in Lysosomal Storage Disorders (LSDs). Mucolipidosis III (ML III) is a LSD caused by GlcNAc-1-phosphotransferase deficiency, which impairs the trafficking of lysosomal hydrolases. 10% of the genetic defects in ML III are splicing mutations, and around 45% affect 5' splice-sites (ss) thus constituting a good target for mutation specific therapies. T...

An Antisense Oligonucletide based therapy for a rare disease: in vitro and in v...

Mucolipidosis 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 subcutaneous adipose tissue from HFE-knockout mice accumulates high levels ...

Assessing meaning violations in Syrian refugees: A mixed-methods cross-cultural...

Refugees are disproportionately affected by extreme trauma events capable of violating core beliefs and life goals, (i.e., global meaning), and causing significant distress. This mixed-methods study used an exploratory sequential design to assess meaning violations in a sample of Syrian refugees living in Portugal. For this purpose, we cross-culturally adapted the Global Meaning Violations Scale (GMVS) for use ...

Desenvolvimento de uma versão portuguesa do nutritional risk screening NRS 2002

The Nutritional Risk Screening (NRS 2002) is a tool that was developed by the Danish Society for Parenteral and Enteral Nutrition. It is a valid system that allows the detection of the risk of undernutrition or of undernutrition in hospitalized individuals and is applied by health professionals. A Portuguese language version of NRS 2002 was developed with linguistic and cultural equivalence to the original usin...

Development of RNA based approaches to exploit alternative therapies for Lysoso...

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...

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...

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 ...

Correction of a Splicing Mutation Affecting an Unverricht-Lundborg Disease Pati...

Unverricht-Lundborg disease (ULD) is a common form of progressive myoclonic epilepsy caused by mutations in the cystatin B gene (CSTB) that encodes an inhibitor of several lysosomal cathepsins. Presently, only pharmacological treatment and psychosocial support are available for ULD patients. To overcome the pathogenic effect of the ULD splicing mutation c.66G>A (exon 1), we investigated whether an antisense oli...