February 1, 2012

Treatment window for genetic disorder

Treatment with a drug used to prevent organ rejection partially reverses the course of tuberous sclerosis, research in mice suggests.

Tuberous sclerosis complex (TSC) is a relatively common genetic disorder that causes benign tumors (hamartomas) to form in many different organs, including the brain. These brain lesions can lead to seizures, autism, cognitive, and behavioral disorders. Mutations in two genes – TSC1 or TSC2 – are responsible for almost all cases.


In the January issue of Neurobiology of Disease, Kevin Ess, M.D., Ph.D., and colleagues show that mice genetically engineered to lack Tsc1 in the brain die prematurely, have increased brain size, and have various anatomical and cellular abnormalities in both neurons and glia (the supporting cells in the brain). Additionally, activity of the “mammalian target of rapamycin complex” (mTORC1 and mTORC2) pathways was altered in brain cells, and treatment with rapamycin (a drug commonly used to combat organ rejection) prevented premature death and reversed glial abnormalities. The results suggest that a postnatal treatment window may exist for combating some of the neurological and cognitive effects of TSC.

The research was supported by the National Institute of Neurological Disorders and Stroke, the Tuberous Sclerosis Alliance, and the Vanderbilt Kennedy Center for Research on Human Development.