Brain dystrophin restoration improves memory in mdx mice

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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 optimized tricyclo DNA antisense by intracerebroventricular injection to correct the reading frame of the mutated exon 23 of the dystrophin mRNA.
  • This method allowed to partially restore the expression of brain dystrophin (from 10 to 30% of the levels of control mice) depending on the brain regions and the dose used.
  • This restoration was maximal in the hippocampus (30%) with a dose of 400µg.
  • The peak of dystrophin production occurred six to seven weeks after the injection.
  • The object recognition test during this optimal treatment period shows that long-term memory was preserved in the treated mice in agreement with the high presence of restored dystrophin in the hippocampus.
  • The fear conditioning test shows that there is no effect on associative learning and a slight improvement in memory retention associated with aversive stimuli. These results can be explained by the weak restoration of dystrophin in the amygdala, a central structure in fear conditioning and aversive memory in general.

 

Partial Restoration of Brain Dystrophin and Behavioral Deficits by Exon Skipping in the Muscular Dystrophy X-Linked (mdx) Mouse. Faouzi Zarrouki, Karima Relizani, Flavien Bizot et al. ANN NEUROL 2022;92:213–229

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