Discovery of glycogen synthase inhibitors for validation as a novel therapeutic target for adult polyglucosan body disease (APBD)
Awardee: Wyatt Yue
Institution: Newcastle University, UK
Grant Amount: $99,025
Funding Period: February 1, 2022 - January 31, 2023
Summary:
Adult polyglucosan body disease is caused by a defective gene encoding glycogen branching enzyme GBE1, resulting in its low activity. The GBE1 enzyme is essential for making glycogen very compact inside the cell, otherwise the glycogen that is being synthesised by another enzyme glycogen synthase GYS1 will form clogging clumps. Drug development programmes for APBD and related diseases have largely sought to deliver an artificial version of the GBE1 gene, or turn down the native GYS1 gene, both emerging gene therapy approaches that remain experimental and costly for the long run. Our vision is to develop a daily pill for APBD patients as a transformative oral therapy. In the first step towards this goal, we aim to develop small molecules that act on the GYS1 enzyme as a drug starting point. To achieve this, we will take advantage of our unique knowledge about the shape of GYS1 enzyme, as well as cutting-edge computational and screening methods to find small molecules.