Therapeutics for Primary Open Angle Galucoma

Track Code: 
Selective heat shock protein 90 (Hsp90) and glucose regulated protein 94 (Grp94) inhibitors that can be used to develop an effective therapy for treating primary open angle glaucoma (POAG).
POAG is the most common form of glaucoma, affecting about three million Americans, and is caused by mutations in myocilin. Mutant myocilin misfolding and aggregation in trabecular meshwork cells causes a toxic gain-of-function, namely, cell death, which hastens an increase in intraocular pressure, a primary risk factor in glaucoma.
Primary open angle glaucoma (POAG)
How it works: 
Through selectively targeting the endoplasmic reticulum chaperone Grp94 using siRNA knockdown or small molecule inhibitors, mutant myocilin can be removed in an efficient manner. Additionally, analogous inhibition of the paralog Hsp90 is under investigation as a therapeutic approach for a variety of diseases including cancer and Alzheimer's disease. The potential benefits of this treatment offers a significant effort towards understanding and preventing this disease.
Effective treatment of myocilin related glaucomas; facilitates clearance of aggregated myocilin proteins
Why it is better: 
Current efforts to devise a treatment strategy for myocilin glaucoma have focused on increasing the secretion of mutant myocilin from the endoplasmic reticulum (ER). This is expected to increase chaperone activity for the mutant myocilin, so that it can be effectively cleared by ER-associated degradation (ERAD). However, research has shown that this method of therapy is at best ineffectual and at worst detrimental, and may require further study. Our inventors have developed a novel strategy that holds considerable promise for treating myocilin glaucoma.
Other Applications: 
anti-cancer, anti-inflammatory, and immunosuppressive activity
Licensing Associate: 
Aswini Betha, PhD · · 913-588-5713
Brian Blagg
US 8,685,966
US 9,045,434