N-Methyl-D-Aspartate Receptors, Ketamine, and Rett Syndrome: Something Special on the Road to Treatments?

      In 2007, Adrian Bird and his colleagues at the University of Edinburgh published a groundbreaking study demonstrating that Rett syndrome (RTT), a severe genetic neurodevelopmental disorder, is reversible in mouse models of the disease (
      • Guy J.
      • Gan J.
      • Selfridge J.
      • Cobb S.
      • Bird A.
      Reversal of neurological defects in a mouse model of Rett syndrome.
      ). Using Cre-Lox technology, the Bird group engineered a mouse in which the disease-causing gene, Mecp2, could be reversibly inactivated. Animals born with the gene switched off—a condition that mimics the loss of MECP2 function that underlies the human disease—developed full-blown symptoms of murine RTT. However, when the gene was reactivated in these severely ill mice, neurological dysfunction was reversed to a significant degree. This remarkable finding demonstrated that even prolonged loss of Mecp2 function does not lead to irreversible changes in brain structure or function, consistent with postmortem studies demonstrating the absence of neuronal cell loss or neurodegeneration in RTT patients. Against the backdrop of these encouraging results, there has been a flurry of activity in recent years to develop pharmacologic interventions that could achieve what Bird’s group had accomplished through genetic engineering in mice, i.e., symptom reversal in RTT.
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