Efficient therapy for refractory Pompe disease by mannose 6-phosphate analogue grafting on acid α-glucosidase.

Pompe disease is a rare disorder due to deficiency of the acid α-glucosidase (GAA) treated by enzyme replacement therapy. The present authorized treatment with rhGAA, the recombinant human enzyme, provides an important benefit in the infantile onset; however, the juvenile and adult forms of the disease corresponding to >80% of the patients are less responsive to this treatment. This resistance has been mainly attributed to an insufficiency of mannose 6-phosphate residues in rhGAA to address lysosomes through the cation-independent mannose 6-phosphate receptor (CI-M6PR).

Pharmacological modulation of LMNA SRSF1-dependent splicing abrogates diet-induced obesity in mice.

Unlabelled: Bakground/Objectives:Intense drug discovery efforts in the metabolic field highlight the need for novel strategies for the treatment of obesity. Alternative splicing (AS) and/or polyadenylation enable the LMNA gene to express distinct protein isoforms that exert opposing effects on energy metabolism and lifespan. Here we aimed to use the splicing factor SRSF1 that contribute to the production of these different isoforms as a target to uncover new anti-obesity drug.

Prevalence of otitis media with effusion in children with allergic rhinitis, a cross sectional study.

Objectives: Otitis media with effusion (OME) may be caused by various factors including Eustachian tube dysfunction, inflammatory response as well as atopy. Allergic rhinitis (AR), a common chronic disorder in children, is associated with swelling of the mucosa and can therefore result in Eustachian tube dysfunction. This study aims to compare the prevalence of OME in subjects with and without AR.

Long lasting control of viral rebound with a new drug ABX464 targeting Rev - mediated viral RNA biogenesis.

Background: Current therapies have succeeded in controlling AIDS pandemic. However, there is a continuing need for new drugs, in particular those acting through new and as yet unexplored mechanisms of action to achieve HIV infection cure. We took advantage of the unique feature of proviral genome to require both activation and inhibition of splicing of viral transcripts to develop molecules capable of achieving long lasting effect on viral replication in humanized mouse models through inhibition of Rev-mediated viral RNA biogenesis.