PDF(Pubmed)
Abstract：
Neurodevelopment is a highly organized and complex process involving lasting and often irreversible changes in the central nervous system. Inherited disorders of neurotransmission (IDNT) are a group of genetic disorders where neurotransmission is primarily affected, resulting in abnormal brain development from early life, manifest as neurodevelopmental disorders and other chronic conditions. In principle, IDNT (particularly those of monogenic causes) are amenable to gene replacement therapy via precise genetic correction. However, practical challenges for gene replacement therapy remain major hurdles for its translation from bench to bedside. We discuss key considerations for the development of gene replacement therapies for IDNT. As an example, we describe our ongoing work on gene replacement therapy for succinic semialdehyde dehydrogenase deficiency, a GABA catabolic disorder.
摘要：
神经发育是一个高度有组织和复杂的过程，涉及中枢神经系统的持久且通常不可逆的变化。遗传性神经传递障碍（IDNT）是一组遗传性疾病，其中神经传递主要受到影响，导致早期大脑发育异常，表现为神经发育障碍和其他慢性疾病。原则上,IDNT（特别是单基因原因的那些）适合通过精确的遗传校正进行基因替代疗法。然而,基因替代疗法的实际挑战仍然是其从长凳到床边翻译的主要障碍。我们讨论了IDNT基因替代疗法开发的关键考虑因素。作为一个例子,我们描述了我们正在进行的琥珀酸半醛脱氢酶缺乏症基因替代疗法的工作，GABA分解代谢紊乱.
