Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Royal Children's Hospital, Melbourne, VIC 3052, Australia.
Electrical and Biomedical Engineering, School of Engineering, RMIT University, Melbourne, VIC 3000, Australia.
Int J Mol Sci. 2024 Oct 7;25(19):10768. doi: 10.3390/ijms251910768.
Pediatric genetic epilepsies, such as CDKL5 Deficiency Disorder (CDD), are severely debilitating, with early-onset seizures occurring more than ten times daily in extreme cases. Existing antiseizure drugs frequently prove ineffective, which significantly impacts child development and diminishes the quality of life for patients and caregivers. The relaxation of cannabis legislation has increased research into potential therapeutic properties of phytocannabinoids such as cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). CBD's antiseizure properties have shown promise, particularly in treating drug-resistant genetic epilepsies associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and Tuberous Sclerosis Complex (TSC). However, specific research on CDD remains limited. Much of the current evidence relies on anecdotal reports of artisanal products lacking accurate data on cannabinoid composition. Utilizing model systems like patient-derived iPSC neurons and brain organoids allows precise dosing and comprehensive exploration of cannabinoids' pharmacodynamics. This review explores the potential of CBD, THC, and other trace cannabinoids in treating CDD and focusing on clinical trials and preclinical models to elucidate the cannabinoid's potential mechanisms of action in disrupted CDD pathways and strengthen the case for further research into their potential as anti-epileptic drugs for CDD. This review offers an updated perspective on cannabinoid's therapeutic potential for CDD.
儿科遗传性癫痫,如 CDKL5 缺乏症(CDD),严重致残,极端情况下每天发作超过十次。现有的抗癫痫药物通常无效,这对儿童的发育和患者及护理人员的生活质量都有重大影响。大麻法规的放宽增加了对植物大麻素(如大麻二酚 (CBD) 和 Δ9-四氢大麻酚 (THC))潜在治疗特性的研究。CBD 的抗惊厥特性显示出希望,特别是在治疗与 Lennox-Gastaut 综合征 (LGS)、Dravet 综合征 (DS) 和结节性硬化症 (TSC) 相关的耐药遗传性癫痫方面。然而,针对 CDD 的具体研究仍然有限。目前的大部分证据依赖于缺乏大麻素成分准确数据的手工制品的轶事报告。利用患者来源的 iPSC 神经元和脑类器官等模型系统,可以精确给药并全面探索大麻素的药效动力学。本综述探讨了 CBD、THC 和其他痕量大麻素在治疗 CDD 中的潜力,并重点介绍了临床试验和临床前模型,以阐明大麻素在 CDD 途径中断中的潜在作用机制,并为进一步研究其作为 CDD 的抗癫痫药物的潜力提供依据。本综述提供了关于大麻素治疗 CDD 潜力的最新观点。