Saoudi, A.; Barberat, S.; le Coz, O.; Vacca, O.; Doisy Caquant, M.; Tensorer, T.; Sliwinski, E.; Garcia, L.; Muntoni, F.; Vaillend, C.; Goyenvalle, A. Partial restoration of brain dystrophin by tricyclo-DNA antisense oligonucleotides alleviates emotional deficits in mdx52 mice

Molecular Therapy – Nucleic Acids, Volume 32, 2023.

Lay Summary

The publication titled “Partial Restoration of Brain Dystrophin by Tricyclo-DNA Antisense Oligonucleotides Alleviates Emotional Deficits in mdx52 Mice” presents a study on the use of a type of antisense oligonucleotide similar to the one in use to induce exon skipping in Duchenne muscular dystrophy (DMD) clinical trials, called tricyclo-DNA, to restore the expression of dystrophin, a protein that is deficient in a DMD mouse model. The researchers investigated the effect of this antisense oligonucleotide administered directly into the fluid around the brain and its impact on emotional deficits in these mice. They found that treatment with tricyclo-DNA antisense oligonucleotides partially restored the production of dystrophin in the brain of the mdx52 mice and improved emotional deficits which are found in this mouse model, and which resemble those commonly associated with DMD. 

DMD is a genetic disorder that primarily affects muscles, including those in the heart and respiratory system, leading to progressive muscle weakness and functional impairment. However, in a proportion of individual with DMD, there can be some difficulties with cognitive and emotional functions, including deficits in emotional processing and social behaviour. 

The study demonstrates that treatment with tricyclo-DNA antisense oligonucleotides resulted in partial restoration of dystrophin in the brain of mdx52 mice, and this restoration was associated with improvements in emotional deficits, including anxiety-like and social behaviour deficits. These findings suggest that restoring dystrophin in the brain using tricyclo-DNA antisense oligonucleotides may have potential therapeutic effects on emotional deficits in DMD, highlighting a novel approach for treating the emotional aspects of this disease.