Treatment with the immunosuppressive drug rapamycin may have a therapeutic effect in patients with Pretzel syndrome, a rare neurodevelopmental disorder (Sci. Trans. Med. 5, 182ra53).

Pretzel syndrome is characterized by epilepsy, cognitive delay and a series of neuroanatomical abnormalities. The disease is caused by mutations in LYK5, which encodes an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1). In mice, loss of Lyk5 affects neuronal migration and leads to the formation of clusters of misplaced neurons in the cortex similar to those observed in patients with Pretzel syndrome.

Whitney Parker et al. found that mTORC1 inhibition with rapamycin can prevent the cortical malformations caused by Lyk5 depletion in the mouse. As rapamycin also prevented a migration defect found in fibroblasts from patients with Pretzel syndrome, the authors treated five patients with rapamycin and reported that this resulted in a reduction in seizure frequency.

Although these findings need to be replicated in a larger cohort in a blinded trial, the results raise the possibility that mTORC1 inhibition may be useful for treating patients with this neurodevelopmental condition.