Neurofibromatosis type 1 Disease Model

Neurofibromatosis type 1 (NF1), a rare autosomal dominant RASopathy caused by mutations in the neurofibromatosis type 1 gene (NF1), affects approximately 1 in 3500 individuals worldwide. Although the neurofibromas associated with the disease are typically benign and can often be surgically resected, some plexiform lesions can lead to significant complications due to encroachment into nearby tissues. Over time, NF1 patients develop skeletal abnormalities, cardiac defects, learning disabilities, and neurological complications, such as seizures and uncontrolled migraines. Additionally, benign lesions may transform into malignant peripheral nerve sheath tumors (MPNSTs) in 10% of NF1 patients, which is associated with poor prognosis. One of the biggest hurdles for patients with NF1 is early detection of both benign neurofibromas and their transformation to MPNSTs. The aim of this study, in collaboration with researchers at the University of Iowa, University of Arizona, and Exemplar Genetics, is to utilize a swine model with a common mutation in NF1 to facilitate early detection of tumors. After initial characterization of the animal model through neurobehavior testing, MR and CT imaging, and pathological assessment of lesions, we plan on using a multi-faceted approach to track the early emergence of neurofibromas and MPNSTs, using MR and CT imaging, biomarker detection, and retrospective analyses. Furthermore, the animal model may prove to be a useful tool for understanding mechanisms of neurofibromin action and for exploring novel drug therapies, particularly for pain management.