#apaperaday from Erlangen where I will present in the Tom Wahlig HSP meeting later today. The pick is from @JAMANetworkOpen by Hong et al on the characteristics of Duchenne patients commercially treated with exon skipping drugs doi 10.1001/jamanetworkopen.2023.53094 The FDA approved eteplirsen in 2016 based on its ability to skip exon 51 to restore the production of partially functional dystrophin. The approach is mutation specific and other exon skipping drugs followed: golodirsen, viltolarsen and casimersen.

#apaperaday Duchenne themed as I read it during the Duchenne Parent Project Belgium meeting last weekend. It is an update on a clinical trial with stem cells in 3 Duchenne patients in Poland. DOI: 10.1007/s12015-023-10620-3 The authors describe that all approved Duchenne therapies currently are suboptimal. Agreed. They offer cell transplantation as a potential solution. However, currently delivery of stem cells is a problem and also the immune response to donor stem cells.

#apaperaday Today’s pick is from @LiebertPub @OTSociety journal Nucleic Acid Therapeutics by Hammond et al from Matthew Wood’s group. It will be published in a special issue in NAT dedicated to “negative results”. Though of course with well done science any result moves science. The paper describes the use of alternatives for phosphorothioate (PS) as ASO backbones for splice switching ASOs. This backbone increases stability and cell uptake but leads to safety issues. Model ASO used here is nusinersen (spinraza, approved for spinal muscular atrophy).

#apaperaday Today’s pick is published in @FASEBorg journal by Chu et al on the long term effects of expression of a mini-dystrophin in an mdx mouse background. Duchenne is caused by lack of dystrophin. Gene addition therapy aims to restore dystrophin production in muscle and heart by providing a copy of the gene code using adeno-associated viral vectors (AAV). However, AAV capacity is too small for complete dystrophin.