Novel emulsion-based formulation of the anti-glaucoma MSH-1001 for improved topic


Principal Investigator: Ronald A Wassel
Abstract: DESCRIPTION (provided by applicant): This Small Business Innovation project aims to develop an innovative eye drop formulation for the treatment of glaucoma and ocular hypertension. Charlesson has acquired from Danube Pharmaceuticals MSH-1001, a new small molecule compound (previously known as DNB-001 or KR- 31378). MSH-1001 is has both ocular hypotensive and neuroprotectant properties. It is an ATP- sensitive K channel opener. The goal of this project is to demonstrate that an emulsion based eye drop can deliver therapeutic levels of MSH-100, to the aqueous humor with the long term goal (Phase 2) of reducing intraocular pressure in an appropriate animal model of ocular hypertension and conducting the IND-enabling studies supporting a first-on-man study. The goal of this proposal is to 1) Make three different types of emulsion based eye drops that can incorporate MSH-1001. 2) Take the three most promising emulsions that meet all of our criteria (i.e. the desired osmolality, pH, viscosity and droplet size) and test them in-vivo for ocular tolerance and histology in Dutch Belted rabbits. Ocular pharmacokinetic properties of the tolerated formulations will be compared to the pharmacologically active experimental suspension. Eyedrops (one drop of 40 5L/eye) will be administered to Dutch Belted rabbits. At different time points (0.25, 0.5, 1, 2, 4, and 8hrs), eyes will be enucleated following euthanasia. Aqueous humor will then carefully be dissected and The MSH- 1001 quantified by LC-MS. The successful ophthalmic emulsion will show ocular distribution at least equal or superior to the experimental suspension. PUBLIC HEALTH RELEVANCE: Glaucoma is primarily treated by administering drugs to decrease intraocular pressure (IOP). Prostaglandins are commonly used to lower IOP by increasing the uveoscleral outflow as first-line therapy. Despite their robust efficacy, many patients often require multiple medications, or glaucoma surgery in the cases refractory to pharmacological treatments, to achieve target pressure control. There is a highly need to develop novel potent IOP lowering drugs so that ophthalmologists can more effectively achieve a better control of the target pressure in those patients. Research has been focused on identifying novel molecular targets with the potential to better the current therapies as a stand-alone or an adjunct to the first-line prostaglandin. The goal of this proposal is to develop a clinical ophthalmic emulsion of MSH-1001, a novel small molecule that effectively lowers IOP by enhancing the trabecular outflow through a novel mechanism of action,. .
Funding Period: 2011-09-01 - 2012-08-31
more information: NIH RePORT