Discovery to Launch of Anti-allergy (Emadine; Patanol/Pataday/Pazeo) and Anti-glaucoma (Travatan; Simbrinza) Ocular Drugs, and Generation of Novel Pharmacological Tools Such as AL-8810

Abstract

The eye and eyesight are exquistly designed and are precious, and yet we often take them for granted. Good vision is critical for our long-term survival and for humanity's enduring progress. Unfortunately, since ocular diseases do not culminate in lifeand-death scenarios, awareness of the plight of millions of people suffering from such eye ailments is not publicized as other diseases. However, losing eyesight or falling victim to visual impairment is a frightening outlook for most people. Glaucoma, a collection of chronic optic neuropathies, of which the most prevalent form, primary open-angle glaucoma (POAG), is the second leading cause of irreversible blindness. POAG currently afflicts >70 million people worldwide and is an insidious, progressive, silent thief of sight that is asymptomatic. On the other hand, allergic conjunctivitis (AC), and the associated rhinitis ("hay-fever"), frequently victimizes a huge number of people worldwide, especially during seasonal changes. While not life-threatening, sufferers of AC soon learn the value of drugs to treat their signs and symptoms of AC as they desire rapid relief to overcome the ocular itching/pain, redness, and tearing AC causes. Herein, I will describe the collective efforts of many researchers whose industrious, diligent, and dedicated team work resulted in the discovery, biochemical/ pharmacological characterization, development and eventual launch of drugs to treat AC (e.g., olopatadine [Patanol/Pataday/Pazeo] and emedastine [Emedine]), and for treating ocular hypertension and POAG (e.g., travoprost [Travatan ] and Simbrinza). This represents a personal perspective.

Recently Approved Drugs for Lowering and Controlling Intraocular Pressure to Reduce Vision Loss in Ocular Hypertensive and Glaucoma Patients

“…The major contributor to this has been the advent and acceptance of a key modifiable biomarker that triggers appropriate treatment initiation, namely elevated IOP [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 104 , 105 ]. With this came the creation, validation, and deployment of numerous types of animal models of OHT (natural and induced) [ 7 , 126 , 127 , 222 , 223 , 224 , 225 , 226 ] to permit screening of potential ocular hypotensive drug candidates. While translation of many such agents has lagged behind, a number of new clinically viable drugs with high enough therapeutic indices have emerged to which patients have responded with acceptable tolerability and efficacy.…”

Therapeutic Drugs and Devices for Tackling Ocular Hypertension and Glaucoma, and Need for Neuroprotection and Cytoprotective Therapies

“…Since it is important to determine whether the test compounds achieve appropriate engagement of the target receptor/enzyme, functional cell/tissue-based assays need to be employed. Human and/or non-human primate ocular cells and tissues, or cells expressing human cloned receptors or enzymes, should be used whenever possible, to have appropriate linkage to the human disease Sharif, 2020a;Sharif, 2020b). Ideally, isolated and well characterized human CM (Sharif et al, 2003a), TM (Sharif et al, 2003b; and NPCE ) cells, or bovine TM cells (Mao et al, 2012), or strips of human/animal ocular tissues (Wiederholt et al, 2000;Rosenthal et al, 2005;Ohia et al, 2018;Njie-Mbye et al, 2018) or ex-vivo models (e.g., Sharif et al, 2009;Sharif et al, 2014b) should be used for testing and characterizing ocular hypotensive compounds.…”