The potential of antisense oligonucleotide therapies for inherited childhood lung diseases.

Antisense oligonucleotides are an emerging therapeutic option to treat diseases with known genetic origin. In the age of personalised medicines, antisense oligonucleotides can sometimes be designed to target and bypass or overcome a patient's genetic mutation, in particular those lesions that compromise normal pre-mRNA processing. Antisense oligonucleotides can alter gene expression through a variety of mechanisms as determined by the chemistry and antisense oligomer design. Through targeting the pre-mRNA, antisense oligonucleotides can alter splicing and induce a specific spliceoform or disrupt the reading frame, target an RNA transcript for degradation through RNaseH activation, block ribosome initiation of protein translation or disrupt miRNA function. The recent accelerated approval of eteplirsen (renamed Exondys 51™) by the Food and Drug Administration, for the treatment of Duchenne muscular dystrophy, and nusinersen, for the treatment of spinal muscular atrophy, herald a new and exciting era in splice-switching antisense oligonucleotide applications to treat inherited diseases. This review considers the potential of antisense oligonucleotides to treat inherited lung diseases of childhood with a focus on cystic fibrosis and disorders of surfactant protein metabolism

Gene transfer to skeletal muscle using hydrodynamic limb vein injection: current applications, hurdles and possible optimizations

International audienc

Unusual localisation of tophaceous gout. A report of four cases and review of the literature

We report four cases with very unusual manifestations of tophaceous gout. All patients were male, aged between 29 and 67 years. Only one patient had an acute gouty arthritis in his medical history, whereas the other three had never developed clinical symptoms from their hyperuricemia. Two patients had gout tophi in the patella, while the others showed gout tophi in the space of bipartite bones, one in a bipartite patella and one in a tripartite sesamoid bone of the first toe. To our knowledge, gout tophi in the space of bi- or tripartite bones has never been described befor

Osteonecrosis of the Talus

Osteonecrosis of the talus (ONT) refers to the death of osteocytes and subsequent structural changes leading to talus collapse and secondary ankle joint osteoarthritis. ONT is a rarer disease than osteonecrosis of the femoral head (ONFH); however it is a signifi cant clinical challenge with an uncertain long-term prognosis [ 1, 2 ]. In this chapter, we review osteonecrosis of the talus, describing incidence and etiology, blood supply, clinical presentation, diagnostic imaging, classifi cation, and treatment.N