Porphyrias are metabolic disorders that are caused by alterations of enzymes involved in heme biosynthesis, leading to a buildup of porphyrins in the body. Porphyrias are grouped into those that predominantly affect the nervous system and those that affect the liver; acute hepatic porphyria, for which there is currently no treatment, can lead to cirrhosis and hepatocellular cancer.
Description
Inhibiting beta-catenin in porphyria targets multiple components of the heme biosynthesis pathway, including early enzymes ALA-S and ALA-D. This prevents buildup of porphyrin intermediates, including HO-1, preventing further heme depletion. The loss of these toxic porphyrins results in decreased protein aggregation, leading to less damage to the liver in beta-catenin inhibited mice. Previous attempts at treating acute hepatic porphyria only targets ALA-S; in contrast, targeting beta-catenin will have multiple wide-ranging downstream affects, representing a unique therapeutic opportunity to treat porphyria.
Applications
· Treating acute hepatic porphyria
Advantages
· Targets an earlier point in the heme biosynthesis pathway, enabling a more comprehensive and therapeutic range of therapeutic effects
Invention Readiness
In vivo data
IP Status
https://patents.google.com/patent/US10961534B2
