Saoudi, A.; Fergus, C.; Gileadi, T.; Montanaro, F.; Morgan, J.E.; Kelly, V.P.; Tensorer, T.; Garcia, L.; Vaillend, C.; Muntoni, F.; Goyenvalle, A. Investigating the Impact of Delivery Routes for Exon Skipping Therapies in the CNS of DMD Mouse Models.

Cells 2023, 12, 908.

Lay Summary

The publication titled “Investigating the Impact of Delivery Routes for Exon Skipping Therapies in the CNS of DMD Mouse Models” presents a study evaluating different delivery routes for exon skipping therapies in the central nervous system (CNS) of mouse models of Duchenne muscular dystrophy (DMD). DMD is a genetic disorder that causes progressive muscle weakness due to the lack of a protein called dystrophin. Exon skipping therapies are experimental treatments that aim to restore functional dystrophin in muscle by skipping certain genetic mutations in the dystrophin gene, based on the use of small synthetic molecules called antisense oligonucleotides. 

The researchers investigated different routes to deliver these antisense oligonucleotides to the brain to optimize the potential of exon skipping therapies in DMD mouse models. They found that direct injection into the lateral ventricles of the CNS resulted in high levels of exon skipping in the brain of DMD mouse models. 

The study demonstrates that the route of delivery is an important factor in the effectiveness of exon skipping therapies in the CNS of DMD mouse models. Direct injection into the CNS appears to be an effective method for achieving high exon skipping levels that could translate in dystrophin restoration in the brain. This is particularly important as DMD is known to affect not only muscles but also the CNS, with a proportion of affected individuals having learning and/ or behavioural difficulties. These findings may contribute to the development of improved delivery strategies for exon skipping therapies in the treatment of DMD and other genetic disorders that affect the CNS. 

This paper has been reviewed by Prof Annemieke Aartsma-Rus in her #paperaday series on Twitter. An overview of this review can be found on the website of the World Duchenne Organization.