Neuron：新药可逆转实验鼠脆性X染色体综合征症状

4月12日，美国麻省理工学院等机构的研究人员在国际杂志《神经元》Neuron上报告说，他们研制出一种新药，可成功逆转患脆性X染色体综合征实验鼠的部分症状。这一研究为此类遗传病患者带来治疗希望。

脆性X染色体综合征是由于人体内X染色体形成过程中突变所导致的常见遗传病，也是孤独症和智力迟钝最普遍的遗传病因。临床主要表现为中、重度智力低下，例如学习能力缺失、认知障碍等，此外还伴有特异的身体和行为特征。目前，该病在男性中的发病率约为四千分之一，女性发病率约为六千分之一，在人类所有种族中均有发病。

在新研究中，研究人员给患有脆性X染色体综合征的成年实验鼠服用新研制的代谢型谷氨酸受体5抑制剂—CTEP。尽管已处于成年阶段，在接受治疗后，实验鼠的学习和记忆能力均有所提高，患病所导致的容貌异常等也有所改善。

研究人员说，这项研究最重要的意义在于证实了脆性X染色体综合征的很多症状并非由不可逆的大脑发育中断所致，修正受损的谷氨酸信号可以带来显著好转。（生物谷Bioon.com）

doi:10.1016/j.neuron.2012.03.009
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Chronic Pharmacological mGlu5 Inhibition Corrects Fragile X in Adult Mice

Aubin Michalon, Michael Sidorov, Theresa M. Ballard, Laurence Ozmen, Will Spooren, Joseph G. Wettstein, Georg Jaeschke, Mark F. Bear, Lothar Lindemann

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability. Previous studies have implicated mGlu5 in the pathogenesis of the disease, but a crucial unanswered question is whether pharmacological mGlu5 inhibition is able to reverse an already established FXS phenotype in mammals. Here we have used the novel, potent, and selective mGlu5 inhibitor CTEP to address this issue in the Fmr1 knockout mouse. Acute CTEP treatment corrects elevated hippocampal long-term depression, protein synthesis, and audiogenic seizures. Chronic treatment that inhibits mGlu5 within a receptor occupancy range of 81% 4% rescues cognitive deficits, auditory hypersensitivity, aberrant dendritic spine density, overactive ERK and mTOR signaling, and partially corrects macroorchidism. This study shows that a comprehensive phenotype correction in FXS is possible with pharmacological intervention starting in young adulthood, after development of the phenotype. It is of great interest how these findings may translate into ongoing clinical research testing mGlu5 inhibitors in FXS patients.