HIF1 Activators as Therapeutics for Triosephosphate Isomerase Deficiency (TPI Df)
University of Pittsburgh researchers have identified several triazines that activate HIF1 and increase TPI expression, offering a potential therapeutic approach for Triosephosphate Isomerase Deficiency (TPI Df). This rare genetic disorder currently has no treatments, making this discovery particularly significant. The researchers are exploring the use of existing HIF1 activators, including PHD inhibitors like vadadustat, to treat TPI Df, with plans to partner with pharmaceutical companies for clinical trials. The use of existing HIF1 activators, such as vadadustat, roxadustat and daprodustat, accelerates the development process, as these compounds have already been approved for other indications.
Description
The technology involves the use of triazines and other HIF1 activators to increase TPI expression, potentially providing a therapeutic benefit for TPI Df patients. Triazines were previously identified as HIF1 activators, and their chemical space has been partially explored. Researchers examined known HIF1 activators, including PHD inhibitors, and found that several compounds, such as vadadustat, directly increase TPI levels. Vadadustat is already approved for use in the US and EU for treating anemia associated with chronic kidney disease (CKD), and the researchers aim to repurpose it for TPI Df treatment.Applications
• Treatment of Triosephosphate Isomerase Deficiency (TPI Df)• Potential repurposing of existing HIF1 activators for rare genetic disorders