Raghavan Kadalraja, Ikewaki Nobunao, Preethy Senthilkumar, Abraham Samuel J K
Department of Paediatric Neurology, Jesuit Antonyraj memorial Inter-disciplinary Centre for Advanced Recovery and Education (JAICARE), Madurai, India.
Department of Medical Life Science, Kyushu University of Medical Sciences, Japan.
Front Genet. 2025 Jun 9;16:1569289. doi: 10.3389/fgene.2025.1569289. eCollection 2025.
Duchenne muscular dystrophy (DMD): is a rare, life-limiting genetic disorder for which no curative treatment currently exists. While various gene therapy approaches, some approved and others still under clinical investigation have been explored, they have not consistently produced the desired outcome and, in some cases, have been associated with serious adverse effects, including mortality. A critical factor we wish to highlight is the hostile inflammatory environment inherent to skeletal muscles' pathology in DMD, which may be further aggravated by gene therapy, either due to the viral vector used or the gene component itself. Therefore, a comparative and detailed evaluation of inflammatory biomarkers between control and treatment arms in such clinical trials is essential to determine whether therapeutic benefits are being compromised by inflammation. Based on the implications of such hostile environment on the therapeutic outcome, adding a safer and efficacious management strategy to mitigate the inflammation during gene therapies is considered indispensable. Therefore, we recommend further research on adjuvant anti-inflammatory approaches to ensure safety and improvement of the therapeutic outcome of gene therapies for DMD.
杜氏肌营养不良症（DMD）：是一种罕见的、危及生命的遗传性疾病，目前尚无治愈性治疗方法。虽然已经探索了各种基因治疗方法，其中一些已获批准，另一些仍在临床研究中，但它们并未始终产生预期的效果，在某些情况下，还与包括死亡在内的严重不良反应相关。我们希望强调的一个关键因素是DMD骨骼肌病理中固有的不利炎症环境，基因治疗可能会因所用的病毒载体或基因成分本身而使其进一步恶化。因此，在此类临床试验中对对照组和治疗组之间的炎症生物标志物进行比较和详细评估，对于确定治疗效果是否因炎症而受到损害至关重要。基于这种不利环境对治疗结果的影响，在基因治疗期间添加一种更安全、有效的管理策略以减轻炎症被认为是必不可少的。因此，我们建议进一步研究辅助抗炎方法以确保DMD基因治疗的安全性并改善治疗效果。
