NF1 is a common, inherited disorder that can have a profound impact on patients' lives. There is currently no effective medical therapy for NF1. NF1-related tumors (neurofibromas) are unusual in that they are composed of more than one type of cell: Schwann cells, which have lost both copies of the Nf1 tumor suppressor gene, and surrounding "stromal" cells, which have lost one copy of this gene. One of these surrounding "stromal" cell types, mast cells, come from the bone marrow and migrates to the site of the tumor. Because the mast cells have lost one copy of the Nf1 gene, they are particularly prone to migrate to the tumor and, once there, to secrete substances that further incite Schwann cells to grow. We think that if we could repair the defective Nf1 gene in these mast cells, NF1-prone mice (and, we hope, people) would not develop neurofibromas because their mast cells would now be normal. We think we can do this by taking skin cells from an NF1-prone mouse and converting them to stem cells (induced progenitor stem [iPS] cells). This conversion, while not yet routine, has been done by dozens of laboratories around the world in the last year. Once we have converted the NF1 skin cells to iPS cells, we can use conventional methods to repair the damaged Nf1 gene, convert the cells into an early form of blood cell, and transplant it back into an NF1 mouse. Such a mouse will now have normal mast cells and should not get sick.

If this approach works, it could open an entirely new chapter in the treatment of NF1. It is a high-risk, high-reward type of project.