McBride Sean M, Bell Aaron J, Jongens Thomas A
Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Results Probl Cell Differ. 2012;54:83-117. doi: 10.1007/978-3-642-21649-7_6.
This chapter will briefly tie together a captivating string of scientific discoveries that began in the 1800s and catapulted us into the current state of the field where trials are under way in humans that have arisen directly from the discoveries made in model organisms such as Drosophila (fruit flies) and mice. The hope is that research efforts in the field of fragile X currently represent a roadmap that demonstrates the utility of identifying a mutant gene responsible for human disease, tracking down the molecular underpinnings of pathogenic phenotypes, and utilizing model organisms to identify and validate potential pharmacologic targets for testing in afflicted humans. Indeed, in fragile X this roadmap has already yielded successful trials in humans (J. Med. Genetic 46(4) 266-271; Jacquemont et al. Sci Transl Med 3(64):64ra61), although the work in studying these interventions in humans is just getting underway as the work in model organisms continues to generate new potential therapeutic targets.
本章将简要梳理一系列引人入胜的科学发现，这些发现始于19世纪，推动我们进入了该领域的当前状态，即基于果蝇和小鼠等模式生物的发现，直接开展人体试验。希望脆性X综合征领域的研究工作目前所呈现的路线图，能够证明鉴定导致人类疾病的突变基因、探寻致病表型的分子基础以及利用模式生物鉴定和验证潜在药理学靶点以供患病人类测试的实用性。事实上，在脆性X综合征方面，这一路线图已经在人体试验中取得了成功（《医学遗传学杂志》46(4) 266 - 271；雅克蒙特等人，《科学转化医学》3(64):64ra61），尽管随着模式生物的研究持续产生新的潜在治疗靶点，对这些干预措施的人体研究工作才刚刚起步。
