Rinshō shinkeigaku = Clinical neurology
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Neuropathic pain is a debilitating pain that occurs after nerve injury and is generally resistant to currently available treatments including morphine. Such pain involves aberrant excitability in dorsal horn neurons after nerve injury. Emerging evidence indicate that the enhanced activity of dorsal horn neurons requires a communication with microglia. ⋯ The mechanisms of microglia activation are unknown, but our recent study shows that interferon-gamma (IFN-gamma) can be an important factor that causes spinal microglia activation after nerve injury. IFN-beta upregulates P2X4R in microglia and causes P2X4R-dependent allodynia. These findings suggest that purinoceptors in spinal microglia is crucial for pathological intractable pain.
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RNA interference (RNAi) is the process of sequence-specific, post-tanscriptional gene silencing, initiated by double-stranded RNA (dsRNA). The gene therapy for familial ALS with siRNA had been started and showed promising results in the model mouse. There is a recent progress in the delivery of siRNA to the central nervous system. There are still important problems for application of gene therapy including off-target effect and gene delivery of siRNA, but a rapid progress can be expected because of the extremely high efficiency of siRNA.
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Duchenne muscular dystrophy (DMD) is caused by the lack of dystrophin protein at the sarcolemma. Exon skipping by antisense oligonucleotides is a novel method to restore the reading frame of the mutated DMD gene, and rescue dystrophin production. ⋯ We also tried systemic delivery of antisense Morpholino to skip exon 51 in mdx52 mice. It is important to verify the effectiveness and side effects of antisense Morpholino in experimental animal models such as dystrophic dogs or mdx52 mice, before clinical trials in DMD patients.