Scientists led by Dr. Pamela Ting have reported the discovery and characterization of the first molecular glue degraders of the WIZ transcription factor for fetal hemoglobin derepression in Sickle Cell Disease, which means a pill-based therapy for humans could begin development.

Sickle Cell Disease is a genetic life-threatening condition caused by mutation in β-hemoglobin. Inducing fetal hemoglobin safely has been the goal for years but has remained out-of-reach. The discovery of dWIZ-1 and dWIZ-2 molecular glue degraders of the WIZ transcription factor that induce HbF in erythroblasts is a milestone toward a pill for therapy. The authors say WIZ is a previously unknown repressor of HbF.

The authors went through a chemical library of molecular glues targeting the protein cereblon to explore fetal hemoglobin (HbF) reactivation and had success with transcription factor WIZ in mice and non-human monkeys.



Science is one thing, of course, and regulatory approval is another. Mice are not little people and monkeys, while biologically closer, are still not enough. There is a billion dollars in clinical trials and unknown government hurdles before this can go to market. It could be decades before it sees pharmacies unless a political appointee tells FDA to give it an emergency use exemption assuming safety and dosing, as the Trump administration did to try and mitigate the COVID-19 pandemic in 2020.