The Experts below are selected from a list of 54 Experts worldwide ranked by ideXlab platform
Peter K. Kaiser - One of the best experts on this subject based on the ideXlab platform.
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VEGF inhibitors for the treatment of neovascular age-related macular degeneration
Expert opinion on investigational drugs, 2009Co-Authors: Mark R. Barakat, Peter K. KaiserAbstract:Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world for those patients aged 50 years or older. Neovascular AMD, a subtype characterized by the growth of new, pathologic blood vessels, results in most of the cases of severe and rapid vision loss associated with AMD. A critical activator of angiogenesis in neovascular AMD is VEGF. Several therapies have been and are now being developed for neovascular AMD, with the goal of inhibiting VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full-length antibodies ranibizumab and bevacizumab, VEGF receptor decoy VEGF Trap, small interfering RNA-based therapies Bevasiranib and AGN211745, sirolimus, and tyrosine kinase inhibitors including vatalanib, pazopanib, TG100801, TG101095, AG013958 and AL39324. At present, established therapies have met with great success in reducing the vision loss associated with neovascular AMD, whereas those still investigational in nature offer the potential for further advances.
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Neovascular Age-Related Macular Degeneration
Drugs, 2008Co-Authors: Aimee V. Chappelow, Peter K. KaiserAbstract:Age-related macular degeneration (AMD) affects an estimated 14 million people worldwide, and is the leading cause of severe, irreversible vision loss in individuals over the age of 50 years in Western societies. Choroidal neovascularization (CNV), the hallmark of ‘wet’, ‘exudative’ or ‘neovascular’ AMD, is responsible for approximately 90% of cases of severe vision loss due to AMD. Vascular endothelial growth factor (VEGF) has been shown to play a key role in the regulation of CNV and vascular permeability. Ranibizumab, the current gold standard in the US for the treatment of neovascular AMD, exerts its effect through binding and inhibition of all isoforms of VEGF. Randomized controlled clinical trials have established ranibizumab as the first US FDA-approved therapy for neovascular AMD to result in improvement in visual acuity. Despite impressive outcomes, treatment with ranibizumab requires sustained treatment regimens and frequent intravitreal injections. In this review, we discuss promising emerging therapies for neovascular AMD that aim to improve outcomes, safety and treatment burden through novel mechanisms of action. Currently in phase III clinical trials, VEGF Trap is a receptor decoy that targets VEGF with higher affinity than ranibizumab and other currently available anti-VEGF agents. Another promising therapeutic strategy is the blockade of VEGF effects by inhibition of the tyrosine kinase cascade downstream from the VEGF receptor; such therapies currently in development include vatalanib, TG100801, pazopanib, AG013958 and AL39324. Small interfering RNA technology-based therapies have been designed to downregulate the production of VEGF (Bevasiranib) or VEGF receptors (AGN211745) by degradation of specific messenger RNA. Other potential therapies include pigment epithelium-derived factor-based therapies, nicotinic acetylcholine receptor antagonists, integrin antagonists and sirolimus.
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Neovascular Age-Related Macular Degeneration: Potential Therapies
Drugs, 2008Co-Authors: Aimee V. Chappelow, Peter K. KaiserAbstract:Age-related macular degeneration (AMD) affects an estimated 14 million people worldwide, and is the leading cause of severe, irreversible vision loss in individuals over the age of 50 years in Western societies. Choroidal neovascularization (CNV), the hallmark of 'wet', 'exudative' or 'neovascular' AMD, is responsible for approximately 90% of cases of severe vision loss due to AMD. Vascular endothelial growth factor (VEGF) has been shown to play a key role in the regulation of CNV and vascular permeability. Ranibizumab, the current gold standard in the US for the treatment of neovascular AMD, exerts its effect through binding and inhibition of all isoforms of VEGF. Randomized controlled clinical trials have established ranibizumab as the first US FDA-approved therapy for neovascular AMD to result in improvement in visual acuity. Despite impressive outcomes, treatment with ranibizumab requires sustained treatment regimens and frequent intravitreal injections. In this review, we discuss promising emerging therapies for neovascular AMD that aim to improve outcomes, safety and treatment burden through novel mechanisms of action. Currently in phase III clinical trials, VEGF Trap is a receptor decoy that targets VEGF with higher affinity than ranibizumab and other currently available anti-VEGF agents. Another promising therapeutic strategy is the blockade of VEGF effects by inhibition of the tyrosine kinase cascade downstream from the VEGF receptor; such therapies currently in development include vatalanib, TG100801, pazopanib, AG013958 and AL39324. Small interfering RNA technology-based therapies have been designed to downregulate the production of VEGF (Bevasiranib) or VEGF receptors (AGN211745) by degradation of specific messenger RNA. Other potential therapies include pigment epithelium-derived factor-based therapies, nicotinic acetylcholine receptor antagonists, integrin antagonists and sirolimus.
Philip J. Rosenfeld - One of the best experts on this subject based on the ideXlab platform.
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Anti-vascular endothelial growth factor therapy for neovascular ocular diseases other than age-related macular degeneration.
Current opinion in ophthalmology, 2009Co-Authors: Thomas A. Ciulla, Philip J. RosenfeldAbstract:Purpose of review Anti-vascular endothelial growth factor (anti-VEGF) therapies that arrest choroidal angiogenesis and reduce vascular permeability have revolutionized clinical practices for neovascular eye diseases. This review describes anti-VEGF strategies that are being evaluated in ocular diseases, other than neovascular age-related macular degeneration, in which neovascularization plays a critical role in pathogenesis. Recent findings Early studies of the anti-VEGF agents, pegaptanib sodium, ranibizumab, bevacizumab, VEGF trap, and Bevasiranib in the treatment of various neovascular diseases (e.g., diabetic macular edema, retinal vein occlusion, choroidal neovascularization) have shown promising results. The efficacy and safety of these agents, either alone or combined with standard treatments (e.g., laser photocoagulation), anti-inflammatory agents, or other non-VEGF-based antiangiogenic therapies, is actively investigated. Non-VEGF-driven pathways and growth factors other than VEGF may play important roles in pathogenesis and are included in certain combination therapies with VEGF inhibitors. Summary The discovery of VEGF-A's role in the pathogenesis of neovascular ocular disease provided a strong rationale for the development of anti-VEGF-based therapies. There is now ample evidence that anti-VEGF therapies are viable treatment options for these diseases. Nevertheless, large, randomized controlled trials are still awaited to confirm early safety and efficacy findings from small, open-label prospective studies.
Shaymaa S. Mousa - One of the best experts on this subject based on the ideXlab platform.
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Current Status of Vascular Endothelial Growth Factor Inhibition in Age-Related Macular Degeneration
BioDrugs, 2010Co-Authors: Shaker A. Mousa, Shaymaa S. MousaAbstract:Angiogenesis, the process by which new vessels are created from pre-existing vasculature, has become the subject of intense research in recent years. Increased rates of angiogenesis are associated with several disease states, including cancer, age-related macular degeneration (AMD), psoriasis, rheumatoid arthritis, and diabetic retinopathy. Vascular endothelial growth factor (VEGF) is an important modulator of angiogenesis, and has been implicated in the pathology of a number of conditions, including AMD, diabetic retinopathy, and cancer. AMD is a progressive disease of the macula and the third major cause of blindness worldwide. If not treated appropriately, AMD can progress to involve both eyes. Until recently, the treatment options for AMD have been limited, with photodynamic therapy (PDT) the mainstay of treatment. Although PDT is effective at slowing disease progression, it rarely results in improved vision. Several therapies have been or are now being developed for neovascular AMD, with the goal of inhibiting VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full-length antibodies ranibizumab and bevacizumab, the VEGF receptor decoy aflibercept, small interfering RNA-based therapies Bevasiranib and AGN 211745, sirolimus, and tyrosine kinase inhibitors, including vatalanib, pazopanib, TG 100801, TG 101095, AG 013958, and AL 39324. At present, established therapies have met with great success in reducing the vision loss associated with neovascular AMD, whereas those still under investigation offer the potential for further advances. In AMD patients, these therapies slow the rate of vision loss and in some cases increase visual acuity. Although VEGF-inhibitor therapies are a milestone in the treatment of these disease states, several concerns need to be addressed before their impact can be fully realized.
Ali Mohammad Tamaddon - One of the best experts on this subject based on the ideXlab platform.
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modulated cellular delivery of anti vegf sirna Bevasiranib by incorporating supramolecular assemblies of hydrophobically modified polyamidoamine dendrimer in stealth liposomes
International Journal of Pharmaceutics, 2016Co-Authors: Nasim Golkar, Soliman Mohammadi Samani, Ali Mohammad TamaddonAbstract:A novel lipopolymer based system was designed and characterized for cellular delivery of anti-VEGF siRNA in SKBR-3 breast tumor cell line. Polyamidoamine (PAMAM) dendrimers of low generations (G1, G2 and G3) were incorporated into polyethylene glycol (PEG)-stabilized liposomes by following the consecutive steps: (a) synthesis of the cholesterol conjugates (40% molar ratio of cholesterol to primary amines of PAMAM), (b) incorporation of the conjugates in liposome by lipid mixing and (c) microencapsulation of the siRNA using the ethanol drop method. The cholesterol conjugates of PAMAM dendrimers (G1-Chol40%, G2-Chol40% and G3-Chol40%) formed self assembly with low CMC values (<11μg/ml). Not only did G2-Chol40% show the highest lipid mixing among the cholesterol conjugates, but also, had the lowest leakage of encapsulated carboxyfluorescein tracer. Various N(amine))/L(lipid)/P(phosphate) mole ratios were investigated for siRNA condensation by ethidium bromide dye exclusion assay. The optimum N/L/P ratio of 20:33:10 was chosen for microencapsulation of anti-VEGF siRNA by ethanol drop method, showing particle size of 130nm, zeta-potential of +4mV, siRNA loading efficiency and capacity of 96% and 13wt%, and high stability against heparin sulfate (extracellular matrix). TEM shows uniform and discrete oligo- or multi-lamellar vesicular structures. The liposome incorporating G2-Chol40% was successfully internalized into SKBR-3 cells mainly through clathrin-mediated endocytosis, which was able to escape from endosomes and showed a significantly higher sequence-specific inhibition of VEGF expression and cell growth than the respective G2-Chol40%/siRNA dendriplexes. Importantly, the cytotoxicity decreased with incorporation of G2-Chol40% in the liposomes.
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Modulated cellular delivery of anti-VEGF siRNA (Bevasiranib) by incorporating supramolecular assemblies of hydrophobically modified polyamidoamine dendrimer in stealth liposomes.
International journal of pharmaceutics, 2016Co-Authors: Nasim Golkar, Soliman Mohammadi Samani, Ali Mohammad TamaddonAbstract:A novel lipopolymer based system was designed and characterized for cellular delivery of anti-VEGF siRNA in SKBR-3 breast tumor cell line. Polyamidoamine (PAMAM) dendrimers of low generations (G1, G2 and G3) were incorporated into polyethylene glycol (PEG)-stabilized liposomes by following the consecutive steps: (a) synthesis of the cholesterol conjugates (40% molar ratio of cholesterol to primary amines of PAMAM), (b) incorporation of the conjugates in liposome by lipid mixing and (c) microencapsulation of the siRNA using the ethanol drop method. The cholesterol conjugates of PAMAM dendrimers (G1-Chol40%, G2-Chol40% and G3-Chol40%) formed self assembly with low CMC values (
Shaker A. Mousa - One of the best experts on this subject based on the ideXlab platform.
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Bevasiranib for the Treatment of Wet, Age-Related Macular Degeneration
Ophthalmology and eye diseases, 2010Co-Authors: Adinoyi O. Garba, Shaker A. MousaAbstract:Age- related Macular Degeneration (AMD) is the leading cause of severe visual impairment in people 65 years and older in industrialized nations. Exudative, or "wet", AMD is a late form of AMD (as distinguished from atrophic, so-called dry, AMD) and is responsible for over 60% of all cases of blindness due to AMD. It is widely accepted that vascular endothelial growth factor (VEGF) is a key component in the pathogenesis of choroidal neo-vascularization (CNV), which is a precursor to wet AMD. The current gold-standard for treating wet AMD is the monoclonal antibody fragment ranibizumab (trade name Lucentis), which targets VEGF. Other agents used to treat wet AMD include pegaptanib (Macugen), bevacizumab (Avastin; off-label use), and several other experimental agents. The advent of small interfering RNA (siRNA) has presented a whole new approach to inhibiting VEGF. This article reviews the status of a novel siRNA-based therapeutic, Bevasiranib, for the treatment of wet AMD. Bevasiranib is believed to work by down regulating VEGF production in the retina. Studies in human cell-lines and animal models have shown that VEGF siRNAs are effective in inhibiting VEGF production. Although there is a lack of sufficient published data on human studies supporting the use of Bevasiranib for wet AMD, available data indicates that due to its unique mechanism of action, Bevasiranib might hold some promise as a primary or adjunct treatment for wet AMD.
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Current Status of Vascular Endothelial Growth Factor Inhibition in Age-Related Macular Degeneration
BioDrugs, 2010Co-Authors: Shaker A. Mousa, Shaymaa S. MousaAbstract:Angiogenesis, the process by which new vessels are created from pre-existing vasculature, has become the subject of intense research in recent years. Increased rates of angiogenesis are associated with several disease states, including cancer, age-related macular degeneration (AMD), psoriasis, rheumatoid arthritis, and diabetic retinopathy. Vascular endothelial growth factor (VEGF) is an important modulator of angiogenesis, and has been implicated in the pathology of a number of conditions, including AMD, diabetic retinopathy, and cancer. AMD is a progressive disease of the macula and the third major cause of blindness worldwide. If not treated appropriately, AMD can progress to involve both eyes. Until recently, the treatment options for AMD have been limited, with photodynamic therapy (PDT) the mainstay of treatment. Although PDT is effective at slowing disease progression, it rarely results in improved vision. Several therapies have been or are now being developed for neovascular AMD, with the goal of inhibiting VEGF. These VEGF inhibitors include the RNA aptamer pegaptanib, partial and full-length antibodies ranibizumab and bevacizumab, the VEGF receptor decoy aflibercept, small interfering RNA-based therapies Bevasiranib and AGN 211745, sirolimus, and tyrosine kinase inhibitors, including vatalanib, pazopanib, TG 100801, TG 101095, AG 013958, and AL 39324. At present, established therapies have met with great success in reducing the vision loss associated with neovascular AMD, whereas those still under investigation offer the potential for further advances. In AMD patients, these therapies slow the rate of vision loss and in some cases increase visual acuity. Although VEGF-inhibitor therapies are a milestone in the treatment of these disease states, several concerns need to be addressed before their impact can be fully realized.