Center for Technology Commercialization

Compounds for Therapeutic Intervention of NF Type 1

(CHMC Ref. Id: 2007-0702)

Overview:

Loss of function mutations in the Neurofibromatosis type 1 (NF1) gene result in an autosomal dominant disease that affects approximately 1 of every 3500 live births. Ninety-five percent of patients develop neurofibromas, benign Schwann cell tumors that can associate with nerve endings (dermal) or large nerves (plexiform). Currently, the only treatments for neurofibromas involve surgical removal of tumor tissue and removal of the affected nerve. The most severe manifestation of NF1 disease comes from the progression of plexiform neurofibromas to MPNST in 8-13% of patients. Half of all MPNST arise in NF1 patients. Despite the fact that NF1 is one of the most frequently inherited genetic disorders and that the gene involved in the disease is known, there is currently no effective therapeutic intervention for NF1.

The present invention provides for therapeutic agents that may be used to treat NF1-related disorders or conditions, particularly tumors arising in NF1 patients such as malignant peripheral nerve sheath tumors, benign plexiform tumors, or neurofibromas. Compounds from the GRI chemical compound library were screened against NF1-expressing and NF1 mutant human MPNST cell lines, using in vitro growth assays to identify compounds that affect the growth of an NF1-/- but not an NF1+/+ human MPNST cell line. This resulted in the identification of 4 compounds showing significant differential effects selective for the NF1-/- cells. Further characterization of these compounds is in progress.

Applications: