Diabetic Macular Edema
Diabetic macular edema (DME) is the most common cause of vision loss in diabetic retinopathy, which is prevalent in over 25% of people with diabetes and affects nearly 10 million individuals in the United States.
The standard of care for DME, particularly for eyes with poor visual acuity, is frequent intravitreous injections of inhibitors of vascular endothelial growth factor (VEGF) such as aflibercept, bevacizumab, and ranibizumab. These therapies are expensive and place a significant burden on the patient. An effective oral medication for DME that avoids the necessity of frequent injections into the eye would be a significant advancement.
Inflammasomes in DME
Activation of the inflammasome is now thought to be an important driver of DME. Circulating levels of inflammasome proteins and intraocular levels of inflammasome output cytokines produced via inflammasome activation are elevated in these patients. Inflammasome inhibition has been found to be neuroprotective in multiple animal model of diabetic retinopathy.
A randomized, double-blind, placebo-controlled clinical trial recently reported that oral administration of lamivudine, an FDA approved HIV drug that also inhibits inflammasome activation, significantly improved vision in patients with poor sight due to DME. Unfortunately, lamivudine can have some significant toxicity issues long term and is not suitable as a treatment for DME. Our compound, K9, is a derivative of lamivudine, designed to avoid the toxicities of the parent molecule. A clinical trial of oral K9 in DME is underway.