I am trying to establish novel therapeutic avenues to cure a broad spectrum of rare diseases.
Each rare disease patient potentially benefitting from the therapeutic approach I propose carries a missense mutation in a glycoprotein gene. The mutation impairs fold of the mutate glycoprotein but does not abrogate its function (responsive mutation).
My idea is that modulators of Endoplasmic Reticulum glycoprotein folding Quality Control (ERQC) and/or of Endoplasmic Reticulum Associated Degradation (ERAD) would rescue secretion, restore function and impart therapeutic benefit.
So far, we have successfully demonstrated rescue of secretion of the Q118E mutant of human Trop-2 in mammalian cells in which the gene encoding the ERQC checkpoint (UGGT1) has been deleted. The HsTrop-2 Q118E mutant causes Gelatinous Drop-Like Corneal Dystrophy (GDLD). UGGT1 inhibitors may one day be active ingredients for eye-drops that would alleviate the symptoms of GDLD.