De Paiva C.S.,Baylor College of Medicine |
Schwartz C.E.,Resolvyx Pharmaceuticals |
Gjorstrup P.,Resolvyx Pharmaceuticals |
Pflugfelder S.C.,Baylor College of Medicine
Cornea | Year: 2012
PURPOSE:: Resolvin E1 (RvE1; RX-10001) belongs to a new class of endogenous immunoregulating mediators, originally identified as a metabolite of the omega-3 polyunsaturated fatty acid, eicosapentaenoic acid. Based on its proven efficacy in models of chronic inflammation, this study investigated the efficacy of resolvin E1 in a murine model of dry eye. METHODS:: C57/B6 mice, aged 6 to 8 weeks, were treated with systemic scopolamine and exposed to air draft and low humidity for 16 hours/day for 5 days and allocated to the following groups: unexposed controls, disease controls, treatment with vehicle or RvE1 delivered topically as its methyl ester prodrug, RX-10005, to enhance corneal surface penetration. Treatment was initiated at the time of desiccating stress induction. Treatment efficacy was assessed by corneal permeability using Oregon Green Dextran and by conjunctival goblet cell density using periodic acid-Schiff reagent. RESULTS:: RvE1 reduced the increase in corneal staining by 80% compared with untreated disease controls. Goblet cell density was reduced by 20% in disease controls but fully maintained in the group receiving RvE1. CONCLUSIONS:: RvE1, delivered as its methyl ester prodrug, improved the outcome measures of corneal staining and goblet cell density in this murine model of dry eye, indicating the potential utility of endogenous resolvins and resolvin analogues in the treatment of dry eye.Copyright © 2012 by Lippincott Williams & Wilkins.
Rajasagi N.K.,University of Tennessee at Knoxville |
Reddy P.B.J.,University of Tennessee at Knoxville |
Mulik S.,University of Tennessee at Knoxville |
Gjorstrup P.,Resolvyx Pharmaceuticals |
Rouse B.T.,University of Tennessee at Knoxville
Investigative Ophthalmology and Visual Science | Year: 2013
Purpose. Neuroprotectin D1 (NPD1) is an anti-inflammatory and proresolving lipid mediator biosynthesized from the omega-3-polyunsaturated fatty acid docosahexaenoic acid (DHA). The purpose of this study is to test the therapeutic potential of NPD1 for the treatment of herpes simplex virus (HSV)-induced stromal keratitis (SK) using a mouse model. Methods. C57BL/6 mice were infected ocularly with HSV-1 strain RE. Infected animals were treated topically with methyl ester prodrug NPD1 (300 ng/eye, 5-μL drop). Development of SK lesions, infiltration of inflammatory cells into the cornea, and production of proinflammatory cytokines, chemokines, and angiogenic factors were compared to untreated animals using slit-lamp biomicroscopy, flow cytometry, ELISA, and quantitative PCR (qPCR). Results. Topical administration of NPD1 resulted in a significant reduction in the severity and incidence of SK, as well as the extent of corneal neovascularization in the NPD1-treated animals compared to their untreated counterparts. Infiltration of fewer neutrophils and pathogenic CD4+ T cells into the cornea, along with a lower number of cells that could be induced ex vivo to produce IFN-γ and IL-17, occurred with NPD1 treatment. Additionally, treatment with NPD1 diminished the production of proinflammatory cytokines, chemokines, and angiogenic factors, such as IL-6, CXCL1, CXCL-10, CCL-20, VEGF-A, MMP-2, and MMP-9 in the corneas of infected animals. Importantly, treatment with NPD1 increased the production of the anti-inflammatory cytokine, IL-10. Conclusions. Our novel findings demonstrate that NPD1 treatment could represent a valuable therapeutic approach to control SK lesions. © 2013 The Association for Research in Vision and Ophthalmology, Inc.
Musto A.E.,Louisiana State University |
Gjorstrup P.,Resolvyx Pharmaceuticals |
Bazan N.G.,Louisiana State University
Epilepsia | Year: 2011
Purpose: Temporal lobe epilepsy, one of the most common epilepsy syndromes, is characterized by hippocampal hyperexcitability and progressive seizure susceptibility. Omega-3 fatty acids are involved in neuronal excitability and have anticonvulsant properties. We studied the effect of docosahexaenoic acid (DHA) or its derived lipid mediator, neuroprotectin D1 (NPD1, 10R,17S-dihydroxy-docosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid), in evoked seizures using a rapid kindling model of temporal lobe epilepsy. Methods: DHA or NPD1 was administered in rodents with or without kindling acquisition. Locomotor seizures and evoked epileptiform hippocampal activity immediately after hippocampal stimulations were analyzed. Key Findings: DHA or NPD1 limits hippocampal electrically induced hyperexcitability. Seizures induced by kindling triggered NPD1 synthesis in the hippocampus. Supplying its precursor, DHA, or direct injection of NPD1 into the third ventricle resulted in attenuation of kindling progression and hippocampal hyperexcitability. Significance: The significance of NPD1 in temporal lobe epilepsy could open new pathways for understanding the initiation and propagation of seizures and the role this lipid mediator plays in the neuronal network. © 2011 International League Against Epilepsy.
Lee J.-E.,Case Western Reserve University |
Sun Y.,Pusan National University |
Gjorstrup P.,Pusan National University |
Pearlman E.,Resolvyx Pharmaceuticals
Investigative Ophthalmology and Visual Science | Year: 2015
PURPOSE. To investigate the role of the lipid mediator, resolvin E1 (RvE1), in corneal inflammation. METHODS. The effect of RvE1 on stimulated human corneal epithelial cells (HCECs) and neutrophils, and mouse macrophage was assessed. C57BL/6 mouse corneas were abraded and treated with RvE1 either before or after stimulation with lipopolysaccharide (LPS) and antibiotic-killed Pseudomonas aeruginosa and Staphylococcus aureus. The levels of CXC chemokines in the cornea were quantified, and the presence of neutrophils in corneal infiltrates was detected by immunohistochemistry and by in vivo confocal microscopy. The effect of RvE1 on apoptosis in the corneal epithelium was assessed using the TUNEL assay. RESULTS. RvE1 significantly inhibited cytokine production in HCECs and neutrophils, and mouse macrophages and cornea. The development of corneal infiltrates, specifically neutrophils, in response to stimulation with LPS, P. aeruginosa, and S. aureus was also significantly reduced. There was no apoptotic effect of RvE1 on mouse corneal epithelial cells. CONCLUSIONS. RvE1 inhibits corneal inflammation induced by LPS, Gram negative (P. aeruginosa) and Gram positive (S. aureus) bacteria. These findings indicate that RvE1 as a potential anti-inflammatory therapy for patients with corneal inflammation and also, when given together with antibiotics, for bacterial keratitis. © 2015 The Association for Research in Vision and Ophthalmology, Inc.
Resolvyx Pharmaceuticals | Date: 2013-08-05
The invention relates to methods of treating inflammatory disease comprising administering a compound of formula A, a compound of any one of formulae 1-49 or I-III, a lipoxin compound, or an oxylipin compound.
Resolvyx Pharmaceuticals | Date: 2010-02-05
The invention relates to reducing, preventing or reversing organ damage, reducing and/or preventing stem cell damage and/or death, enhancing organ preservation and/or survival, or enhancing stem cell preservation and/or survival comprising administering a compound of formula A, a compound of any one of formulae 1-49 or I-III, a lipoxin compound, an oxylipin compound, or a combination of aspirin and an omega-3 fatty acid.
News Article | November 20, 2008
Got Dry Eye? Take Fish Oil. Resolvyx Moves First Compound Into Human Test Resolvyx Pharmaceuticals is eying the ophthalmic market. The Bedford, MA-based biotech firm plans to announce today that the first human clinical tests of its resolvins—compounds with anti-inflammatory properties that occur naturally in fish oil—will be in patients with dry eye syndrome. Mind you, many initial clinical trials are done with small pools of 40 or so healthy volunteers to test the safety of drugs. In Resolvyx’s planned trial, however, the firm plans to enroll 200 patients with dry eye to study not only the safety of a resolvin compound, dubbed RX-10045, but its effectiveness at various doses, CEO Paul Rubin says. The so-called Phase 1/2 trial, slated to begin before the end of the year, could also provide data to support later trials in other eye disorders such as age-related macular degeneration. Luke wrote about Resolvyx and its strategy to commercialize resolvins in July, when company officials talked more about use of the compounds in inflammatory disorders such as asthma and rheumatoid arthritis. While the company still plans to begin an initial clinical trial for asthma with a separate resolvin compound by mid-2009, Rubin told me why his company chose to pursue eye disorders first. “I think it’s a little bit easier to do the eye because people aren’t systemically affected by the drug,” Rubin says. “The thing about ophthalmology is you can actually do your first clinical trials with patients rather than just [healthy] volunteers. If the findings are positive, then we have obviously accelerated the timeline for development.” It’s not totally uncommon for drug developers to test novel compounds in peoples’ eyes before trying them inside the body. In fact, some of the earliest clinical trials of RNA-interference drugs have been for eye disorders, such as San Francisco-based Sirna Therapeutics’ early trial to develop the treatments for age-related macular degeneration. The market for dry eye products is huge as well. Resolvyx says that there are between 25 million and 30 million Americans with dry eye syndrome. And in animal tests, the company found that one of the benefits of its resolvin treatment was it prevented loss of mucus-secreting cells that help to keep our eyes lubricated.
News Article | August 24, 2009
Resolvyx, Swinging for the Fence in First Human Study, Passes Test with Drug for Dry Eye Resolvyx Pharmaceuticals, the company that develops derivatives from omega-3 fish oils into new drugs, is announcing today that the first therapy from this class passed its first clinical trial, helping alleviate symptoms for patients with chronic dry eye. This was a big hurdle for Bedford, MA-based Resolvyx to clear, partly because the company set the initial bar unusually high. Most initial clinical trials enroll only a dozen or so patients, assess safety at a number of low doses, then start thinking about effectiveness. But Resolvyx cut to the chase. It is reporting today that its proprietary eye drop was able to achieve a statistically significant reduction in the dryness, stinging, burning, and grittiness sensations in a trial of 232 patients who were randomly assigned to get the drug or a placebo. There were no serious side effects. This is certainly a big step for Resolvyx, because it provides some validation to the company’s claim that its class of compounds, called resolvins, can have potent anti-inflammatory effects. Resolvyx plans to develop oral pill formulas that can be used broadly in common inflammatory diseases like asthma or inflammatory bowel disease. While dry eye doesn’t sound nearly as serious as those conditions, it is one of the most common eye conditions treated by doctors, and is estimated to affect 25 million to 30 million people in the U.S.. “There is an urgent need for new treatment options in dry eye and the results of this Phase 2 study are as strong as any I have seen,” said Stephen Pflugfelder, an expert in dry eye at Baylor College of Medicine, in a company statement. “Based both on these clinical results and on its unique mode of action, I am confident that RX-10045 can be an important new treatment.” Full details haven’t yet been presented in a peer-reviewed journal, although the results are expected to be presented at the Association for Research in Vision and Opthalmology meeting next year, the company says. For the biostatistical sticklers out there, don’t worry, I had a chance to comb through the details with Resolvyx’s chief operating officer James Nichols. But for those who just want the gist, here goes: Resolvyx can’t go quite so far as to say this was an absolute grand slam, but the results are certainly good enough to go ahead with final stage clinical trials, estimated to begin in the first half of 2010. It’s also enticing enough that Resolvyx will now hit the fundraising trail to seek another round from investors, and discuss partnership possibilities with big drugmakers, Nichols says. So what about the details has gotten Resolvyx so excited? The trial looked at … Next Page »
News Article | June 5, 2015
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