Treatment for a neurological disorder in children is all in the genes

A protein called neurofibromin and a competing pathway could be the ticket to a novel gene therapy for a rare pediatric disorder called neurofibromatosis, which is associated with autism and learning difficulties. The proposed therapy could reverse these symptoms, announced officials from the University of Texas (UT) Southwestern on Monday.

Neurofibromatosis, also known as NF1 or Recklinghausen disease, is found in about one in 3,000 people. Mutations in the encoding of neurofibromin and the subsequent loss of that protein in mouse models had a significant impact on the cerebellum, the seat of learning, speech and memory. The disorder is also associated with the proliferation of tumors, since neurofibromin also serves to mitigate tumor growth.

Luis F. Parada, PhD, the chairman of developmental biology and nerve regeneration at UT Southwestern, and her colleagues found a molecule that could counter the effects of this faulty encoding. Preliminary results in mice look promising.

"Children with neurofibromatosis have a high incidence of intellectual deficits and autism, syndromes that have been linked to the cerebellum and cortex," said Parada, in an official statement. "Our findings in these mouse models suggest that despite embryonic loss of the gene, therapies after birth may be able to reverse some aspects of the disease."

Without that neurofibromin, tumors have free reign to grow around nerves—and this is exacerbated by the ERK pathway, which goes into overdrive without the normal checks and balances. This genetic pathway is closely linked to cerebellum defects. The researchers devised an inhibitor for this pathway that could one day be used to treat children with this disorder, if further clinical trials in humans validate these findings.