fig1

Figure 1. Small molecule therapy to correct NF1-haploinsufficiency. In the normal cell (A), two normal NF1 alleles provide a normal level of WT neurofibromin. By contrast, in the NF1^+/- haploinsufficient cell (B), the abnormal NF1 allele does not contribute any WT neurofibromin, resulting in NF1 protein haploinsufficiency, and a disease state. In the treated NF1^+/- cell (C), a drug increases transcription by the normal NF1 allele (red arrow), resulting in increased WT neurofibromin (purple arrows) and correction of haploinsufficiency. Increasing transcription is just one of several methods to increase neurofibromin expression. NF1: Neurofibromatosis type 1; WT: wild-type.