Neurofibromatosis type 1 (NF1) is a genetic disease caused by a mutation of NF1, a gene which normally limits cell proliferation. When one of the two NF1 alleles becomes inactivated, benign tumors called neurofibromas develop and cause various health complications. When this occurs, benign tumors called neurofibromas develop and cause various health complications. In some cases, neurofibromas transform into aggressive life-threatening tumors.
Initial identification of the NF1 gene as causative for the disease created hope that the defect could be corrected using gene therapy strategies. However, genetic correction of NF1 mutations is met with several outstanding issues that render this type of approach unlikely to succeed for the time being. Instead of trying to correct the disease-causing mutation, we propose a new approach in this project to treat NF1 aimed at killing cells that have inactivated both copies of the NF1 gene.
The concept underlying this original therapeutic approach is based on the fact that mutation in one gene often creates vulnerabilities towards inactivation of other genes not normally required for cell survival. In our project, we plan to use a spinoff of the recently developed CRISPR/CAS9 technology to identify genes that become essential for the survival of cells that have inactivated both copies of the NF1 gene. We will then focus on target genes for which an FDA-approved drug is already available. Such a drug, if successful in killing NF1-mutant cells, should quickly become available for clinical testing in NF1 patients.
Investigators
Eric Pasmant, PharmD, PhD
University Paris Descartes
Raphaël Margueron, PhD
Institut Curie
Eric Pasmant, PharmD, PhD
University Paris Descartes
Raphaël Margueron, PhD
Institut Curie