In a study published in May 2022, two French teams succeeded in partially restoring dystrophin in certain brain regions of adult mdx mice, an animal model of Duchenne muscular dystrophy, thereby improving certain cognitive functions affected in the disease.
- The researchers administered optimised tricyclo-DNA antisense by intracerebroventricular injection to correct the reading frame of the mutated exon 23 of the dystrophin mRNA.
- This method enabled partial restoration of cerebral dystrophin expression (10 to 30% of levels in control mice) depending on the brain region and dose used.
- This restoration was maximal in the hippocampus (30%) with a dose of 400µg.
- Peak dystrophin production occurred six to seven weeks after injection.
- The object recognition test during this optimal treatment period showed that long-term memory was preserved in the treated mice, in line with the high presence of restored dystrophin in the hippocampus.
- The fear conditioning test showed no effect on associative learning and a slight improvement in memory retention associated with aversive stimuli. These results can be explained by the low restoration of dystrophin in the amygdala, a central structure in fear conditioning and aversive memory in general.
In a more recent study, the researchers targeted the defective exon of the mRNA of mdx52 mice with a mutation in exon 52, which are more representative of the disease conditions in humans:
- Dystrophin was partially restored from 5 to 15% of normal levels in the hippocampus, cerebellum and cortex. Levels remained stable between seven and eleven weeks after injection.
- The excessive anxiety and fear that characterise mdx52 mice were significantly reduced in the treated animals.
- The treatment completely restored associative learning and improved memory associated with aversive stimuli.
