Related Experiment Video
Updated: Sep 13, 2025
Characterizing Exon Skipping Efficiency in DMD Patient Samples in Clinical Trials of Antisense Oligonucleotides
Published on: May 7, 2020
Electrophysiological Evaluation in mdx52 Mouse Brain After Antisense-Mediated Exon 51 or 53 Skipping
Yasumasa Hashimoto1,2,3, Yoshitsugu Aoki4
1Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan.
Abstract:
Duchenne muscular dystrophy (DMD) is a neuromuscular disease characterized by progressive muscle weakness alongside cognitive and behavioral impairments. Notably, the lack of brain-specific Dp140 isoform increases the risk of neurodevelopmental disorders in DMD. We reported abnormal social behavior and the reduced glutamatergic transmission using electrophysiological techniques in DMD model mice lacking Dp140. Also, we proposed that antisense oligonucleotide (ASO) -induced exon 53 skipping therapy is thought to be promising for neurodevelopmental disorders in DMD lacking Dp140. Here, we describe a detailed protocol for the intracerebroventricular injection and electrophysiological evaluation in the brain of DMD model mice following ASO-induced exon 51 or 53 skipping therapy.
Insights
Duchenne muscular dystrophy (DMD) involves muscle weakness and neurodevelopmental issues due to the missing Dp140 brain protein. This study details a method to test antisense oligonucleotide therapy for these cognitive and behavioral impairments in DMD mice.
Area of Science:
- Neuroscience
- Genetics
- Pharmacology
Background:
- Duchenne muscular dystrophy (DMD) is a severe neuromuscular disorder causing progressive muscle degeneration.
- The absence of the brain-specific Dp140 isoform in DMD patients is linked to cognitive and behavioral deficits.
- Previous studies in DMD model mice lacking Dp140 showed abnormal social behavior and impaired glutamatergic transmission.
Purpose of the Study:
- To establish a detailed protocol for evaluating antisense oligonucleotide (ASO)-induced exon skipping therapy in the brains of DMD model mice.
- To assess the efficacy of ASO therapy targeting exon 51 or 53 for neurodevelopmental disorders in DMD models lacking Dp140.
Main Methods:
- Intracerebroventricular (ICV) injection of ASOs in DMD model mice lacking Dp140.
- Electrophysiological evaluation of synaptic transmission in the brains of treated mice.
- Behavioral assessments to monitor social behavior.
Main Results:
- The study provides a comprehensive protocol for ICV ASO administration and subsequent electrophysiological analysis in DMD mouse models.
- This methodology allows for the investigation of ASO-induced exon skipping effects on neurodevelopmental aspects of DMD.
- The described methods are crucial for advancing therapeutic strategies for DMD-associated neurocognitive impairments.
Conclusions:
- The developed protocol facilitates the assessment of ASO exon skipping therapies for neurodevelopmental disorders in DMD.
- This research supports the potential of ASO therapy to address cognitive and behavioral deficits in DMD patients lacking Dp140.
- Further research utilizing this protocol can optimize ASO strategies for DMD-associated neurological conditions.
