Löscher Wolfgang, Gernert Manuela, Heinemann Uwe
Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Bünteweg 17, 30559 Hannover, Germany.
Trends Neurosci. 2008 Feb;31(2):62-73. doi: 10.1016/j.tins.2007.11.012. Epub 2008 Jan 16.
The past decades have brought several advances to the treatment of epilepsy. However, despite the continued development and release of new antiepileptic drugs (AEDs), more than one-third of patients are resistant to pharmacological treatment. Furthermore, current AEDs do not prevent the development and progression of epilepsy. Thus, there is an urgent need to develop new therapies for AED-resistant patients, for prevention of epilepsy in patients at risk and for disease modification. Cell replacement and gene therapies have been proposed to offer potential approaches for improvements in therapy, but are such approaches really more promising than new pharmacological strategies? Here we critically review and discuss data from epilepsy models and human tissue studies indicating that cell and gene therapies might provide alternative therapeutic approaches for AED-resistant focal epilepsies and might have antiepileptogenic or disease-modifying potential. However, several crucial issues remain to be resolved to develop cell and gene therapies into effective and safe therapies.
在过去几十年里，癫痫治疗取得了多项进展。然而，尽管新型抗癫痫药物（AEDs）不断研发和推出，但仍有超过三分之一的患者对药物治疗耐药。此外，目前的AEDs并不能预防癫痫的发生和进展。因此，迫切需要为耐药患者开发新的治疗方法，预防有风险患者的癫痫发作，并改变疾病进程。细胞替代疗法和基因疗法已被提出，有望改善治疗效果，但这些方法真的比新的药物策略更有前景吗？在此，我们对癫痫模型和人体组织研究的数据进行批判性回顾和讨论，结果表明细胞和基因疗法可能为耐药性局灶性癫痫提供替代治疗方法，并且可能具有抗癫痫发生或改变疾病进程的潜力。然而，要将细胞和基因疗法发展成为有效且安全的疗法，仍有几个关键问题有待解决。
