Therapeutics: Glycogen dependent kinase 3 (GSK3); dyskerin pseudouridine synthase 1 (DKC1)

Patient sample and cell culture studies suggest GSK3 inhibitors could help treat dyskeratosis congenita, which is caused by mutations in DKC1 or other genes that result in shortened telomeres, dysfunction in stem cell proliferation, abnormal skin and nails, intestinal defects, bone marrow failure and other symptoms. In intestinal cells generated from induced pluripotent stem (iPS) cells derived from patients harboring DKC1 mutations or from healthy volunteers that were engineered to express disease-related DKC1 mutations, a GSK3 inhibitor tool compound increased telomerase activity, telomere length and levels of stem cell proliferation and differentiation markers compared with vehicle. Next steps could include testing GSK3 inhibitors in animal models of dyskeratosis congenita.

Noscira S.A. and AMO Pharma Ltd. have tideglusib (AMO-02), a GSK3 inhibitor, in Phase II testing to treat myotonic dystrophy type 1 (DM1)...