Applied Therapeutics is committed to advancing research into the causes of, and treatment for, PMM2-CDG.
Our AT-007 program focuses on the targeted inhibition (or “turning off”) of Aldose Reductase.
Aldose Reductase is the first enzyme in the polyol pathway and converts glucose to sorbitol. Over-activation of the polyol pathway can derange normal metabolic feedback loops and shift balance of complex pathways. PMM2-CDG patients have high levels of sorbitol in their body. It is hypothesized that abnormal Aldose Reductase activity adversely affects PMM2 activity, which then further stimulates Aldose Reductase activity in a feedback loop. Aldose Reductase inhibition blocks the polyol pathway, restoring glucose flow through the hexokinase pathway, increasing PMM2 activity and reducing toxic sorbitol accumulation.
AT-007 has the potential to be the first FDA-approved therapy for PMM2-CDG.