Kuria Technology
Corneal endothelial cells (CECs) form a single layer on the posterior surface of the cornea, and are responsible for maintaining corneal clarity and vision. CECs do not regenerate, and if they are damaged or die, they are gone forever.
Stained corneal cross-section depicting tissue structures and placement
Normal appearance of the corneal endothelial monolayer under specular microscopy
Meeney & Mudhar, Eye 27: 272-276 (2013)
CEC loss can occur acutely, through insults such as ocular surgery, or chronically, from diseases such as Fuchs' endothelial cell dystrophy (FECD). Corneal endothelial disease can lead to visual disturbances such as glare, blurring, and loss of contrast sensitivity, and once CEC density drops below ~500-750 cells/mm2, complete blindness can result.
Acute insult causes step-wise loss
(Trauma, ocular surgeries)
Disease causes chronic loss
(Corneal endothelial dystrophies, diabetes)
Jurkunas et al, Am J Path 177:2278-2289 (2010)
Adapted from Armitage et al, IOVS 44:3326-3331 (2003)
Currently, there are no pharmacologic therapies available to prevent or treat corneal endothelial disease, with corneal transplant often the only option for patients with end-stage corneal disease (ESCD) who have lost their vision.
There is extensive evidence in both surgery-associated CEC loss and in Fuchs' dystrophy that the disease process responsible for CEC dysfunction and loss is driven by impaired mitochondrial function and oxidative stress. Nrf2 is the master regulator of the antioxidant defense system; activation of Nrf2 is associated with improved mitochondrial function, detoxification of free radicals, and decreased inflammatory signaling.
Kuria aims to lead innovation in corneal endothelial health, applying Nrf2 biology across the spectrum of corneal endothelial dysfunction. Our lead development candidate, KTX-1161, is a topical ophthalmic formulation of a novel, potent activator of Nrf2. The active component of KTX-1161 has high solubility and permeability, and in nonclinical studies has been shown to activate Nrf2 in key ocular tissues. Our lead programs target both acute and chronic settings of CEC loss, and we anticipate evaluating additional applications associated with ESCD in the future.