We usually consider medicine as a predictive scientific endeavor, as methodical in application as noble in purpose. But for some diseases, such as schizophrenia, the first treatments showing any effectiveness, including lithium, chlorpromazine, and even electroconvulsive therapy, were discovered entirely by accident. After the discovery of the first antipsychotic treatments, a period of allegedly rational schizophrenia drug development ensued, focusing on drugs that block the brain dopamine receptor DRD2 that was considered, based on very limited evidence, as the critical lock for chemical antipsychotic keys. Some of the drugs worked – more or less, with serious side effects. Truly rational drug development, however, required understanding of the causal basis of disease, which for brain diseases like schizophrenia requires, to a considerable extent, understanding the dark inner workings of the brain itself.
But the causal basis of one relatively-simple brain disease, Fragile X syndrome, has, in the past few months, been deciphered – a true milestone in the touted medical march from brain to computer, lab bench to bedside. Afflicting about 1 in 3000 children, Fragile X is the most-common known cause of both intellectual disability and autism. A series of studies, led by researchers including Gul Dölen and Mark Bear at MIT (Dölen and Bear 2008) and Randi Hagerman at UC Davis (Hagerman et al. 2009), has identified the core neuronal defect caused by mutation of the fragile X gene, and shown they can fix it – literally cure it (Figure 1) – in mice. The fix involves (more…)