New therapeutic targets in the treatment of age-related macular degeneration

Muñoz-Ramón, Pablo; Martínez, P. Hernández; Muñoz‐Negrete, Francisco J.

doi:10.1016/j.oftale.2019.09.013

Cited by 9 publications

(12 citation statements)

References 37 publications

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“…With the biological implications of angiopoietin and approaches described, faricimab (formerly RG7716), is the first bispecific antibody designed for intravitreal use, and can simultaneously bind to and neutralize Ang-2 and VEGF-A for treatment of nAMD and DME [ 16 , 59 , 60 ]. Patients with retinal vascular diseases deemed anti-VEGF sub-responders by retina specialists demonstrate a lack of visual acuity improvement or persistent anatomical symptoms, such as intra- or subretinal fluid.…”

Section: Clinical Studies Of Faricimab In Diabetic Macular Edemamentioning

confidence: 99%

“…Faricimab aims to improve these patients’ prognoses by providing an alternative biological pathway for their treatment by inhibiting both VEGF and Ang-2. By simultaneously binding to both targets, faricimab can provide improved efficacy and durability in patients with DME and durability in nAMD—inherently decreasing treatment burden [ 59 , 60 ], a targeted area of focus for researchers and ophthalmologists.…”

Section: Clinical Studies Of Faricimab In Diabetic Macular Edemamentioning

confidence: 99%

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Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Khan

Aziz

Shafi

et al. 2020

Cells

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This review summarizes the latest findings in the literature of Angiopoietin-2 (Ang-2), Tyrosine-protein kinase receptor (Tie-2) complex, and faricimab along with their involvement for the treatment of retinal vascular diseases in various clinical trials. In ischemic diseases, such as diabetic retinopathy, Ang-2 is upregulated, deactivating Tie-2, resulting in vascular leakage, pericyte loss, and inflammation. Recombinant Angiopeotin-1 (Ang-1), Ang-2-blocking molecules, and inhibitors of vascular endothelial protein tyrosine phosphatase (VE-PTP) decrease inflammation-associated vascular leakage, showing therapeutic effects in diabetes, atherosclerosis, and ocular neovascular diseases. In addition, novel studies show that angiopoietin-like proteins may play an important role in cellular metabolism leading to retinal vascular diseases. Current therapeutic focus combines Ang-Tie targeted drugs with other anti-angiogenic or immune therapies. Clinical studies have identified faricimab, a novel bispecific antibody designed for intravitreal use, to simultaneously bind and neutralize Ang-2 and VEGF-A for treatment of diabetic eye disease. By targeting both Ang-2 and vascular endothelial growth factor-A (VEGF-A), faricimab displays an improved and sustained efficacy over longer treatment intervals, delivering superior vision outcomes for patients with diabetic macular edema and reducing the treatment burden for patients with neovascular age-related macular degeneration and diabetic macular edema. Phase 2 results have produced promising outcomes with regard to efficacy and durability. Faricimab is currently being evaluated in global Phase 3 studies.

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Section: Clinical Studies Of Faricimab In Diabetic Macular Edemamentioning

confidence: 99%

Section: Clinical Studies Of Faricimab In Diabetic Macular Edemamentioning

confidence: 99%

Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Khan

Aziz

Shafi

et al. 2020

Cells

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“…63 In addition, emerging therapies based on gene therapy are setting in as a novel, efficient, and specific antiangiogenic strategy treatment by inducing anti-VEGF endogenous factor expression. 5,77 With this background, BD are being used in AMD or DR, 77,78 and recent efforts are focused on the gene therapy which can be substantially more effective by targeting the disease in its genetic origin and acting at a molecular level by introducing the therapeutic gene which stimulates or inhibits the expression of a protein of interest in the pathology. 52,79 These new therapies are described in following sections.…”

Section: Anti -Veg F Ag Ents For O Cul Ar Neova Scul Ariz Ationmentioning

confidence: 99%

“…These diseases present ocular neovascularization triggered by a pathologic angiogenesis process that involves degradation of the basement membrane, extracellular proteolysis and abnormal blood vessels growth 2,3 . AMD implies choroidal neovascularization as a consequence of hypoxia, ischemia, and inflammation, causing macular thickening and edema 4,5 . In DR, the hyperglycemia seems to have a structural and physiological effect: retinal capillaries become blocked and this results in early stages of the pathology where micro aneurism are formed 6,7 .…”

Section: Introductionmentioning

confidence: 99%

Biological drug therapy for ocular angiogenesis: Anti‐VEGF agents and novel strategies based on nanotechnology

Formica

Alfonso

Palma

2021

Pharmacology Res & Perspec

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Currently, biological drug therapy for ocular angiogenesis treatment is based on the administration of anti‐VEGF agents via intravitreal route. The molecules approved with this purpose for ocular use include pegaptanib, ranibizumab, and aflibercept, whereas bevacizumab is commonly off‐label used in the clinical practice. The schedule dosage involves repeated intravitreal injections of anti‐VEGF agents to achieve and maintain effective concentrations in retina and choroids, which are administrated as solutions form. In this review article, we describe the features of different anti‐VEGF agents, major challenges for their ocular delivery and the nanoparticles in development as delivery system of them. In this way, several polymeric and lipid nanoparticles are explored to load anti‐VEGF agents with the aim of achieving sustained drug release and thus, minimize the number of intravitreal injections required. The main challenges were focused in the loading the molecules that maintain their bioactivity after their release from nanoparticulate system, followed the evaluation of them through studies of formulation stability, pharmacokinetic, and efficacy in in vitro and in vivo models. The analysis was based on the information published in peer‐reviewed published papers relevant to anti‐VEGF treatments and nanoparticles developed as ocular anti‐VEGF delivery system.

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“…It also might increase the possibilities of the success of gene or cell therapy. Several candidates have been tested as neuroprotective factors, including basic fibroblast growth factor (bFGF), brain-derived neurotrophic factor (BNDF), ciliary neurotrophic factor (CNTF), glial cell-derived neurotrophic factor (GNDF) and rod-derived cone viability factor (rdCVF), and all of them have shown increased photoreceptor survival in animal models and humans [ 89 – 91 ].…”

Section: Main Textmentioning

confidence: 99%

Dissecting the role of EYS in retinal degeneration: clinical and molecular aspects and its implications for future therapy

García-Delgado

Valdés-Sánchez

Morillo-Sánchez

et al. 2021

Orphanet J Rare Dis

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Mutations in the EYS gene are one of the major causes of autosomal recessive retinitis pigmentosa. EYS-retinopathy presents a severe clinical phenotype, and patients currently have no therapeutic options. The progress in personalised medicine and gene and cell therapies hold promise for treating this degenerative disease. However, lack of understanding and incomplete comprehension of disease's mechanism and the role of EYS in the healthy retina are critical limitations for the translation of current technical advances into real therapeutic possibilities. This review recapitulates the present knowledge about EYS-retinopathies, their clinical presentations and proposed genotype–phenotype correlations. Molecular details of the gene and the protein, mainly based on animal model data, are analysed. The proposed cellular localisation and roles of this large multi-domain protein are detailed. Future therapeutic approaches for EYS-retinopathies are discussed.

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New therapeutic targets in the treatment of age-related macular degeneration

Cited by 9 publications

References 37 publications

Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Targeting Angiopoietin in Retinal Vascular Diseases: A Literature Review and Summary of Clinical Trials Involving Faricimab

Biological drug therapy for ocular angiogenesis: Anti‐VEGF agents and novel strategies based on nanotechnology

Dissecting the role of EYS in retinal degeneration: clinical and molecular aspects and its implications for future therapy

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