Neurofibromatosis Type 2 (NF2) is a genetic disorder that often results in tumors inside the skull and brain. These tumors, while they frequently grow slowly, are resistant to traditional chemotherapy and cause facial deformities and pain by local compression of the tumors. Furthermore, virtually all NF2 patients eventually experience a complete loss of hearing due to the location of these tumors as they grow in size.

The best way to find drugs that will prevent or destroy these tumors is to create an animal model for testing purposes. Mice are most commonly used for this. The challenge is to find a way to consistently breed mice that mirror the same disease and symptoms that humans have. Our lab, along with our collaborators, has extensive experience in the generation of mouse models to treat this kind of tumor, called plexiform neurofibromas. Working with that model, we were able to develop the first non-surgical treatment for the tumors developed by neurofibromatosis type 1 (NF1) patients. This has led to several successful clinical trials.

We have now created, for the first time, a mouse model that appears to form both intracranial vestibular Schwannomas and meningiomas, the prevalent brain tumors that are found in individuals with neurofibromatosis type 2. We intend to track and analyze chronologically the growth of the tumors found in these mice and determine at which point hearing and balance loss occurs. We will also determine life expectancy once the tumors have developed and will analyze the specific cause of death for mice with NF2 tumors. While other genetically engineered mice with NF2 have been made, they do not form the intracranial tumors that occur in these patients.

Generating and characterizing this model is the first step in identifying the direction we need to take to have an effective preclinical drug screening platform that can assess the relevant human functions (hearing, balance) for the Schwannomas caused by NF2. Given the recent increase in new clinical and research faculty at our institution invested in this disease and our prior experience with NF1, we believe that with this mouse characterized we would be poised to pursue experimental therapeutic testing and then move this work to the clinic.