Children with NF1, a genetic condition, are prone to developing tumors, particularly in the brain and nerves. One of the most common tumors to develop in patients with NF1 is low-grade glioma, which affects the optic pathway and can be associated with a loss of vision or the early onset of puberty. So far, mouse models of these NF-1 associated tumors have been developed. However, mouse models are only of limited use, especially for rapidly discovering and developing drugs. In the project funded by the Gilbert Family Foundation, Jürgen Knoblich and his lab will collaborate with David Gutmann ([Washington University, School of Medicine, Neurofibromatosis Center]) to develop brain organoids into a model for NF1-associated low-grade gliomas.
Brain organoids are a groundbreaking 3D tissue culture system, developed from human induced pluripotent stem cells, which accurately models human-specific aspects of brain development. The Knoblich lab has pioneered the use of human brain organoids to recapitulate neurodevelopmental disorders and tumorigenesis.
In the project funded by the Gilbert Family Foundation, researchers in the Knoblich lab will study the impact of mutations in the NF1 gene on brain tumor development, by developing brain organoids in which the NF1 gene carries mutations found in patients. In particular, the researchers will generate organoids in which the timing of NF1 loss can be monitored. These NF1 glioma models will allow the researchers to study the impact of NF1 mutation on glioma development. These studies will provide critical insights into how brain tumors develop in children with neurofibromatosis type 1 and establish a platform for the discovery and screening of future anti-tumor drugs.
Dan and Jennifer Gilbert have been passionate advocates in the fight to end NF since their oldest son, Nicolas, was born with NF1. They established the Gilbert Family Foundation in 2015 to further advance their NF research efforts.