Abstract
Patients of congenital diseases have abnormalities in their chromosomes and/or genes. Therefore, it has been considered that drug treatments can serve to do little for these patients more than to patch over each symptom temporarily when it arises. Although we cannot normalize their chromosomes and genes with chemical drugs, we may be able to manipulate the amounts and patterns of mRNAs transcribed from patients DNAs with small chemicals. Based on this simple idea, we have looked for chemical compounds which can be applicable for human diseases targeting kinase families of CDKs, CLKs and DYRKs which are involved in the regulation of gene expression, and eventually succeeded to find FIT039, TG003, and ALGERNON as potential therapeutic drugs to cure diseases such as viral infections, Duchenne muscular dystrophy, and Down syndrome, respectively. In addition, we established splicing reporter assay for disease genes with dual color (SPREADD) using a segment of pathogenic genes, and found a splicing modulator, RECTAS, which can rectify the aberrant IKBKAP splicing in Familial dysautonomia patient fibroblasts with SPREADD screening. Our chemical therapeutics are applicable for other congenital diseases such as Fabry disease and Cystic fibrosis.
