Björklund Tomas, Kirik Deniz
Brain Repair and Imaging in Neural Systems, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Biochim Biophys Acta. 2009 Jul;1792(7):703-13. doi: 10.1016/j.bbadis.2009.02.009. Epub 2009 Feb 27.
The ever-evolving understanding of the neuronal systems involved in Parkinson's disease together with the recent advances in recombinant viral vector technology has led to the development of several gene therapy applications that are now entering into clinical testing phase. To date, four fundamentally different approaches have been pursued utilizing recombinant adeno-associated virus and lentiviruses as vectors for delivery. These strategies aim either to restore the lost brain functions by substitution of enzymes critical for synthesis of neurotransmitters or neurotrophic factors as a means to boost the function of remaining neurons in the diseased brain. In this review we discuss the differences in mechanism of action and describe the scientific rationale behind the currently tested gene therapy approaches for Parkinson's disease in some detail and pinpoint their individual unique strengths and weaknesses.
对帕金森病相关神经元系统的认识不断发展，再加上重组病毒载体技术的最新进展，催生了几种基因治疗应用，目前这些应用已进入临床试验阶段。迄今为止，人们采用了四种根本不同的方法，利用重组腺相关病毒和慢病毒作为载体进行递送。这些策略旨在通过替代对神经递质或神经营养因子合成至关重要的酶来恢复丧失的脑功能，以此增强患病大脑中剩余神经元的功能。在本综述中，我们讨论了作用机制的差异，并详细描述了目前针对帕金森病进行测试的基因治疗方法背后的科学原理，明确指出了它们各自独特的优缺点。
