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Neurofibromatosis 2

What is Neurofibromatosis 2?

Neurofibromatosis 2 (NF2) is a rare genetic disorder that affects approximately 1/30,000 individuals globally. NF2 results in the growth of multiple tumors throughout the central and peripheral nervous systems. The cause of these tumors is a defect in the NF2 gene. The NF2 gene encodes for a protein called Merlin. Merlin functions as tumor suppressor that in healthy individuals prevents the growth of tumors.

While usually benign, these tumors result in severe morbidity and mortality in affected individuals. Tumors that grow on the hearing nerves, called vestibular schwannomas, affect almost all NF2 patients and result in hearing loss, severe balance problems, and facial paralysis. Large vestibular schwannomas can also cause death through compression of the brain stem. NF2 patients also frequently experience peripheral neuropathy and vision problems, which, along with the tumors, have a considerable impact on quality of life. While symptoms usually appear in the teenage years, they can occur at any age, even in very young children. NF2 is an autosomal dominant disorder, which means that children of NF2 patients have a 50% chance of inheriting the disorder.

Our therapeutic strategy: Gene replacement

We aim to introduce new copies of the NF2 gene using AAV in order to increase the amount of normal NF2 gene product (Merlin) to a level at which it can execute its tumor suppressor functions in patients. This project involves an international collaboration among several research groups with expertise in either NF2 or gene therapy. The Mueller group will design the project and the gene therapy and do preliminary testing in cells and healthy mice. Other groups that have more expertise in NF2 will treat NF2 mouse models with the gene therapy and examine effects on NF2 pathology.