| Compositions and methods for treating diverticular disease -> Monitor Keywords |
|
|
  Compositions and methods for treating diverticular diseaseUSPTO Application #: 20070254833Title: Compositions and methods for treating diverticular disease Abstract: Agents, compositions, and implants are provided herein for treating diverticular disease (e.g., diverticulosis and diverticulitis). In particular, fibrosis-inducing agents, hemostatic agents, and/or anti-infective agents, or compositions containing one or more of these agents are provided for use in methods for treating diverticular disease. (end of abstract) Agent: Brian R. Woodworth - Lake Forest, IL, US Inventors: William L. Hunter, Philip M. Toleikis, David M. Gravett, Rui Avelar, Dechi Guan USPTO Applicaton #: 20070254833 - Class: 514002000 (USPTO) Related Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai The Patent Description & Claims data below is from USPTO Patent Application 20070254833. Brief Patent Description - Full Patent Description - Patent Application Claims
1. FIELD OF THE INVENTION [0001] The present invention is directed to the fields of ophthalmology and cell biology of vision. Specifically, the present invention regards the treatment, amelioration or prevention of age-related macular degeneration (ARMD), including nonexudative (Dry ARMD) and exudative (Wet ARMD) forms. The present invention encompasses novel compositions and methods to treat ARMD and related eye disorders. In one embodiment, the method utilizes, or the composition comprises, an apolipoprotein A-I Milano (AIM) or a apolipoprotein A-I Milano-lipid complex. 2. BACKGROUND OF THE INVENTION [0002] 2.1 Age-Related Macular Degeneration [0003] Age-related macular degeneration (ARMD) is one of the leading causes of severe visual loss in the developed world (Taylor et al., Br J. Ophtalmol 85:261-266, 2001; VanNewkirk et al., Ophtalmol 107:1593-1600, 2000). In the early stages of the disease, before visual loss occurs from choroidal neovascularization, there is progressive accumulation of lipids in Bruch's membrane (Pauleikhoff et al., PNAS USA 94:4647-4652, 1990; Holz et al., Arch Ophtalmol 112:402-406, 1994; Sheraidah et al., Ophtalmol 100:47-51, 1993; Spaide et al., Retina 19:141-147, 1999). Bruch's membrane lies at the critical juncture between the outer retina and its blood supply, the choriocapillaris. Progressive lipid deposition causes reduced hydraulic conductivity and macromolecular permeability in Bruch's membrane and thereby may impair retinal metabolism (Moore et al., Invenst Optalmol Vis Sci 36:1290-1297, 1995; Pauleikhoffet al., PNAS USA 94:4647-4652,1990; Starita et al., Exp Eye Res 62:565-572, 1996). After sufficient deposition of cholesterol and other lipids in Bruch's membrane, retinal pigmented epithelial cells (RPE) may respond by elaboration of angiogenic factors (e.g. VEGF, vFGF) that promote growth of new vessels from the choroid. [0004] Thus, reduced hydraulic conductivity is one possible explanation for RPE and retina ischemia. The other explanation is the decreased choroidal perfusion, which normally decreases with age and decreases more severely in patient with ARMD. Worsening levels of choroidal perfusion are accosiated with more severe levels of ARMD (Spraul et al., Invest Ophtalmol Vis Sci, 39(11):2201-2202, 1998; Grunwald et al., Invest Ophtalmol Vis Sci, 46(3):1033-1038, 2005; Ciulla et al., Br J Ophtalmol. 86(2):209-213,2002). Also, there is a histologic evidence of choroidal arteriosclerosis (Curcio et al., Invest Ophtalmol Vis Sci, 42:265, 2001). [0005] An open question is the pathogenesis of lipid deposition that ultimately triggers neovascularization. Interestingly, there are parallels between the lipid accumulation in Bruch's membrane found in ARMD and that observed in an animal model of atherosclerosis, the apolipoprotein E (apo E) null mice (Dithmar et al., Invest Ophtalmol Vis Sci., 41:2035-2042, 2000; Kliffen et al., Br J Ophtalmol 84:1415-1419, 2000). Immunohistochemistry on post-mortem eyes has demonstrated apo E in the basal aspect of the retinal pigmented epithelium (RPE) (Anderson et al., Am J Ophtalmol 131)6):767-768, 2001). Cultured RPE cells synthesize high levels of apo E mRNA, comparable to levels found in brain (Anderson et al., 2001, supra). Apolipoprotein E and apo E alleles may be a common denominator associated with several age-related degenerations, for example Alzheimer's disease and atherosclerosis. These associations have stimulated recent investigation of the potential role of apo E in ARMD. Several studies on apo E polymorphism in ARMD have been conducted to find linkages to specific alleles (Simonelli et al., Ophtalmic Res 33:325-328, 2001; Klayer et al., Am J Hum Genet 63(1):200-206, 1998; Souied et al., Am J Ophtalmol 125(3):353-359, 1998). In contrast to Alzheimer's disease, the apo E-4 allele has been associated with reduced prevalence of ARMD. Apo E-2 allele is slightly increased in patients with ARMD. Further supporting a role in ARMD pathogenesis, apo E has been detected in drusens, the Bruch's membrane deposits that are the hallmark of ARMD (Klayer et al., 1998, supra; Anderson et al., 2001, supra). [0006] While the role of apo E in ARMD is suggested but not established, this apolipoprotein has several functions that may affect the course of this disease. Apo E has anti-angiogenic (Browning et al., J Exp Med 180(5): 1949-1954, 1994), anti-inflammatory (Michael et al., in Cellular Immunology, vol. 159, issue 2, pages 124-139, 1994), and anti-oxidative effects (Tangirala et al., E J Biol Chem 276(1): 261-266, 2001). These are all considered atheroprotective attributes of Apo E, but may also be important in protecting against progression of ARMD. While atheroprotective effects of apo E were initially thought to stem from its effects on plasma lipid levels, local effects on vascular macrophages are probably equally important. Thus, selective enhanced expression of macrophage apo E in the arterial wall reduces atherosclerosis in spite of hyperlipidemia (Shimano et al., J Clin Invest 95:469-476, 1995; Bellosta et al., J Clin Invest 96:2170-2177,1995; Hasty et al., Circulation 99:2571-2576, 1999). Conversely, reduction of Apo E levels by reconstitution of apo E null macrophages into C57BL/6 wild type mice fosters the development of atherosclerosis (Fazio et al., 1994). [0007] Atheroprotective effects of arterial apo E expression are thought to derive in part from facilitation of reverse cholesterol transport (Mazzone et al., Circulation 86 (Suppl I): 1-2, 1992; Lin et al., E J Lipid Res 40:1618-1626, 1999). The mechanisms by which apo E facilitates reverse cholesterol transport are incompletely understood. Apo E expression increases cholesterol efflux to HDL3 in J774 macrophages (Mazzone and Reardon, J Lipid Res 35:1345-1353, 1994) and lipid free apolipoprotein Al (Langer et al., J Mol Med 78:217-227, 2000). Cell surface apo E is also hypothesized to induce efflux from the plasma membrane (Lin et al., 1999, supra). [0008] Cholesterol transport may be important in the pathogenesis of ARMD because of lipid efflux from RPE into Bruch's membrane. Very much like intimal macrophages, RPE cells progressively accumulate lipid deposits throughout life; however, unlike vessel wall macrophages, the source of RPE lipid is thought to be retinal photoreceptor outer segments (POS) (Kennedy et al., Eye 9:262-274, 1995). Every day, each RPE cell phagocytoses and degrades more than one thousand POS via lysosomal enzymes. These POS are enriched in phospholipid and contain the photoreactive pigment, rhodopsin. Incompletely digested POS accumulate as lipofuscin in RPE. By age 80, approximately 20% of RPE cell volume is occupied by lipofuscin (Feeney-Burns et al., J Invest Ophtalmol Vis Sci 25:195-200, 1984). [0009] Analysis of Bruch's membrane lipid reveals an age-related accumulation of phospholipid, triglyceride, cholesterol, and cholesterol ester (Holz et al., 1994, supra; Curcio et al., J Invest Ophtalmol Vis Sci 42:265, 2001). The origin of these lipids also is thought to derive principally from POS rather than from the circulation (Holz et al., 1994, supra; Spaide et al., 1999, supra). POS lipids are hypothesized to efflux from the RPE into Bruch's membrane. Although cholesterol ester deposition in Bruch's suggests contribution from plasma lipids, biochemical analysis of these ethers suggests etherification of intracellular cholesterol by RPE cell derived ACAT (Curcio et al., ARVO Abstracts, 2002). While trafficking of lipids from the retina to RPE cells has been studied extensively, mechanisms of lipid efflux from RPE to Bruch's membrane are not well understood. Furthermore, from a pathogenic standpoint, regulation of lipid efflux into Bruch's membrane may be important in determining the rate of lipid-induced thickening that occurs in aging. [0010] The three possible sources for cholesterol in Bruch's membrane include cellular cholesterol and plasma lipids described above, as well as an in situ synthesis. The brain, for example, synthesizes its own cholesterol, obtains very little of it from the plasma, and has a very slow cholesterol turn over. [0011] Reverse cholesterol transport in macrophages is regulated by nuclear hormone receptor ligands via their effects on ABCA-1 and apo E expression. Liver X receptor (LXR) and/or retinoid X receptor (RXR) ligands increase levels of these transporters and increase reverse cholesterol transport in macrophages (Mak et al., J Biol Chem 277(35):31900-31908, 2002; Laffitte et al., PNAS USA 98(2):507-512, 2001). Thyroid hormone has also been demonstrated to increase expression of apo E three fold in HepG2 cells (Laffitte et al., Eur J Biochem 224(2):463-471, 1994). [0012] In atherosclerosis (AS), lipids accumulate in the extracellular matrix and within phagocytic cells, primarily macrophages. Mechanisms of lipid metabolism in AS have been investigated in detail. Similar investigations into lipid processing by RPE and subsequent lipid efflux into BM and the circulation have not been conducted with the same depth as those for AS. As a consequence, potential therapeutic approaches to dry ARMD are wanting. [0013] Mullins (Mullins et al., FASEB J 14(7):835-846, 2000) describes compositional similarity between drusen and other extracellular deposits, including atherosclerotic plaques. Specifically, vitronectin, amyloid P, Apo E and lipids are among the constituents shared in common. More specifically, apolipoprotein E is identified in retinal pigmented epithelium. [0014] Friedman (Friedman, Am J Ophtalmol 130(5):658-663, 2000) reviews the role of atherosclerosis in the pathogenesis of ARMD. Specifically, the review mentions targeting the angiogenesis pathway for treating the neovascular form of ARMD, such as the member VEGF. It is noted that interfering with the upregulation or action of angiogenic agents may prove helpful for choroidal neovascularization, and, in alternative embodiments, statins may be useful for lowering the risk of ARMD. [0015] Anderson et al. (Anderson et al., 2001, supra) reports that apolipoprotein E protein is found in the same location as drusen, likely originating from the retinal pigmented epithelium. [0016] U.S. Pat. No. 6,071,924 regards inhibition of proliferation of retinal pigmented epithelium by contacting RPE cells with a retinoic acid receptor agonist, except for retinoic acid, preferably thereby inhibiting AP-1-dependent gene expression. In specific embodiments, an AP1 antagonist is delivered to a subject in need thereof for inhibition of proliferation of retinal pigment epithelium or a disease associated therewith. [0017] U.S. Pat. No. 6,075,032 is directed to inhibition of choroidal neovascularization by contacting RPE cells with an AP-1 antagonist. [0018] U.S. Pat. No. 5,824,685 regards amelioration of proliferative vitreoretinopathy or traction retinal detachment by contacting RPE cells with a retinoic acid receptor selected from ethyl-6-[2-(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinate, 6-[2-(4,4-dimethylchroman-6-yl) ethynyl]nicotinic acid, and p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)propenyl]-ben- zoic acid. [0019] U.S. Pat. No. 6,372,753 addresses inhibition of an ocular disease resulting from proliferation of retinal pigmented epithelium by providing at least one AP-1 antagonist and at least one retinoic acid receptor (RAR) agonist, except for retinoic acid. [0020] WO 01/58494 is directed to treating or preventing an ocular disease, such as age-related macular degeneration, by contacting an ocular cell with an expression vector comprising a nucleic acid sequence encoding an inhibitor of angiogenesis and a neurotrophic agent. In specific embodiments, the inhibitor of angiogenesis and the neurotrophic agent are one and the same, such as pigment epithelium-derived factor (PEDF). [0021] WO 02/13812 regards the use of an insulin-sensitizing agent, preferably peroxisome proliferator-activated receptor y (PPAR y) agonists, for the treatment of an inflammatory disease, such as an ophthalmic disease. [0022] WO 00/52479 addresses diagnosing, treating, and preventing drusen-associated disorders (any disorder which involves drusen formation), including ARMD. In specific embodiments, there are methods related to providing an effective amount of an agent that inhibits immune cell proliferation or differentiation, such as antagonists of the cytokine, tumor necrosis factor (TNF)-alpha. Continue reading... Full patent description for Compositions and methods for treating diverticular disease Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Compositions and methods for treating diverticular disease patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. Start now! - Receive info on patent apps like Compositions and methods for treating diverticular disease or other areas of interest. ### Previous Patent Application: Compositions and methods for promotion of wound healing Next Patent Application: Compound ws727713 Industry Class: Drug, bio-affecting and body treating compositions ### FreshPatents.com Support Thank you for viewing the Compositions and methods for treating diverticular disease patent info. IP-related news and info Results in 3.36238 seconds Other interesting Feshpatents.com categories: Qualcomm , Schering-Plough , Schlumberger , Seagate , Siemens , Texas Instruments , |
||
