On October 10, a group of Professor Toshifumi Fukuda and Professor Shigeru Yanagi of the Faculty of Life Sciences, Tokyo University of Pharmacy announced that they had succeeded in radically treating autism using mice for the first time.
For psychiatric disorders such as autism, onset factors and treatment methods have been studied at the genetic and molecular levels, but the current situation is that a fundamental treatment method rooted in the cause of the onset has not yet been established. is.
The group created and analyzed mice lacking the gene CAMDI, which is suggested to be involved in the development of developmental disorders and psychiatric disorders.As a result, delayed neuronal migration in the cerebral cortex, which is considered to be one of the causes of developmental disorders, was observed, and this mouse has typical autism-like behavior such as hyperactivity, repetitive behavior, and dysregulation to new environments. Showed action.
In addition, by examining deficient mice, we discovered HDAC6, which is one of the deacetylases, as a binding protein of CAMDI. CAMDI was found to suppress the enzymatic activity of HDAC6 and stabilize the centrosome microtubule skeleton that regulates neuronal migration.
When CAMDI is deficient, HDAC6 is overactivated and the centrosome becomes immature, causing delayed neuronal migration.However, administration of Tubastatin A, an HDAC6-specific inhibitor, during the embryonic period restored nerve cell migration to normal and dramatically restored autism-like behavior.This is the world's first successful example of the radical treatment of autism-like behavior using mice, and it is said to be an epoch-making research result that shows the direction of the next-generation treatment strategy.
Since SAHA (vorinostat), one of the widespread HDAC inhibitors that also inhibits the enzymatic activity of HDAC6, has already been approved as a therapeutic drug for "cutaneous T-cell lymphoma", it can be used as a therapeutic drug for mental diseases by drug repositioning. May be usable.In the future, it is expected that research will be carried out with a view to applying SAHA and that new treatment methods will be established.
