Recent Developments for the Treatment of Glaucoma
Glaucoma is one of the leading causes of irreversible blindness globally, with over 75.0 million people anticipated to be affected in 2020 with that number growing to over 110 million in 2040. The prevalence of glaucoma coupled with the unfortunate realit
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Recent Developments for the Treatment of Glaucoma Christopher M. Adams and Julien P. N. Papillon
Contents 1 Introduction 2 Drug Delivery: Maximizing the Potential of Existing IOP Lowering Molecules 2.1 Extraocular Sustained Release Systems 2.2 Intraocular Sustained Release Systems 3 The Discovery of Novel, Clinical Stage, Low Molecular Weight (LMW) IOP Lowering Therapies 3.1 Rho Kinase Inhibitors 3.2 LIM Domain Kinase 1 (LIMK1) and LIM Domain Kinase 2 (LIMK2) Inhibitors 3.3 Nitric Oxide Donors and sGC Modulators 3.4 Beyond the Prostaglandin F Receptor (FP), Next Generation Prostanoid Receptor Therapies 4 Novel IOP Lowering Therapies in Early Discovery 4.1 Modulators of 5-HT2 Receptors 4.2 Bivalent Melatonin Receptor Agonist and Fatty Acid Amide Hydrolase Inhibitors 4.3 MGL Inhibitors 4.4 KATP Channel Openers 4.5 Adenosine A1 Receptor Agonists 4.6 P2Y6 Receptor Agonists 5 Going Beyond LMW Therapies 6 Neuroprotective Therapies 7 Conclusion References
Abstract Glaucoma is one of the leading causes of irreversible blindness globally, with over 75.0 million people anticipated to be affected in 2020 with that number growing to over 110 million in 2040. The prevalence of glaucoma coupled with the unfortunate reality that the disease still progresses in 30–80% of patients prescribed the standard of care has led to continued interest in glaucoma drug discovery. This
C. M. Adams (*) and J. P. N. Papillon Global Discovery Chemistry, Novartis Institutes for Biomedical Research, Inc., Cambridge, MA, USA e-mail: [email protected]
C. M. Adams and J. P. N. Papillon
chapter reviews advances in glaucoma therapies over the last 5 years. The focus is on: (1) advancements in drug delivery that offer the potential for enhancing the efficacy of current treatments; (2) new and emerging therapies for primary open angle glaucoma (POAG) in both the clinical and pre-clinical stages (the review of emerging glaucoma therapies highlighted in this chapter is limited to those for which in vivo efficacy data were published); and (3) progress toward treating the underlying optic neuropathy, which defines glaucoma. Keywords Aqueous humor, Bamosiran, Bimatoprost, Brimonidine, EP2, Glaucoma, Intraocular pressure (IOP), ISTH0036, Latanoprost, Latanoprostene bunod, LIM domain kinase, Memantine, Netarsudil, Neuroprotection, Ocular hypertension (OHT), Omidenepag, Outflow, Primary open angle glaucoma (POAG), Prostaglandin receptors, Retinal ganglion cells, Rho kinase, Ripasudil, Soluble guanylate cyclase, Sustained release, Taprenepag isopropyl, Trabecular meshwork, Travoprost
1 Introduction Glaucoma is one of the leading causes of irreversible blindness globally, with over 75.0 million people anticipated to be affected in 2020 with that number growing to over 110 million in 2040 [1, 2]. The most prevalent forms of the disease are primary open angle glaucoma (POAG) and primary angle closure glaucoma (PACG), with the incidence rate of POAG nearly double that of PACG [2]. Both diseases are commonly characterized by an increase in intraocular p
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