More than 17 M patients die every year due to cardiovascular diseases. Heart attack and stroke account for the highest number of deaths. Combined together, the disorder accounts for 1 out of every 20 deaths, costing $34 billion annually in USA alone. Prevalence of stroke is predicted to rise by 20.5% from 2012-2030. The two major factors propelling the growth of the acute ischemic stroke diagnosis and treatment market are; large patient population and a rise in population at a higher risk of developing stroke in the near future. Rising incidence of diabetes along with heavy tobacco users and an increase in the ageing population are significant risk factors that can increase the patient population.
Tissue plasminogen activator (tPA-alteplase) is the only FDA approved drug currently used for stroke patients. The drug is not effective beyond 3hr treatment window and works by dissolving the blood-clot formed. Brain edema is a significant complication that arises following stroke.
AQP4 is a bidirectional water specific channel protein and is highly expressed in brain and upregulated in edema and related pathologies. AQP4 is principally responsible for water influx in the brain edema. Brain edema is the result of increased permeability of water channel protein-AQP4. AQP4 levels are increased following ischemia- such as cerebral ischemia (stroke); myocardial ischemia (heart attack) and Retinal ischemia (diabetic macular edema) to name a few.
There are no drugs available specifically targeting water channel protein Aquaporin- 4 (AQP-4) in the brain. Existing drugs to prevent brain edema either do not work or act indirectly. Clinically useful inhibitors of AQP4 are yet to be developed. Our structure based screening of a small molecule library based on 3D AQP-4 protein crystal structure has yielded potent compounds for which we have filed for patent protection.