CNS Research and Early Clinical Development, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
Trends Pharmacol Sci. 2012 Dec;33(12):669-84. doi: 10.1016/j.tips.2012.09.004. Epub 2012 Oct 18.
Autism and autism spectrum disorders (ASDs) affect millions of individuals worldwide. Despite increased autism diagnoses over the past 30 years, therapeutic intervention is often 'trial and error'. This approach has identified some beneficial agents, but complex heterogeneous disorders require a more personalized treatment regimen. Many ASD risk factors are genetic, implicating impaired synaptic development and function. Monogenetic disorders (e.g., fragile X syndrome, Rett syndrome, and neurofibromatosis) that have phenotypic overlap with autism provide insights into ASD pathology through the identification novel drug targets (e.g., glutamatergic receptors). Encouragingly, some of these novel drug targets provide symptomatic improvement, even in patients who have lived with ASDs for protracted periods of time. Consequently, a targeted drug discovery approach is expected to deliver improved agents for the treatment and management of ASDs. Here, we review the opportunities and challenges in drug development for autism and provide insight into the neurobiology of ASDs.
自闭症谱系障碍（ASD）影响着全球数以百万计的人。尽管过去 30 年来自闭症的诊断有所增加，但治疗干预往往是“反复试验”。这种方法已经确定了一些有益的药物，但复杂的异质疾病需要更个性化的治疗方案。许多自闭症风险因素是遗传的，这暗示着突触发育和功能受损。具有与自闭症表型重叠的单基因疾病（如脆性 X 综合征、雷特综合征和神经纤维瘤病）通过鉴定新的药物靶点（如谷氨酸能受体）为自闭症病理提供了见解。令人鼓舞的是，其中一些新的药物靶点提供了症状改善，即使是那些患有自闭症很长时间的患者。因此，预计靶向药物发现方法将为自闭症的治疗和管理提供更好的药物。在这里，我们综述了自闭症药物开发的机遇和挑战，并深入了解了自闭症的神经生物学。
