Imatinib and other ABL inhibitors to treat ocular neovascularisation
Available for: Exclusive Licensing
Retinal and choroidal diseases are the most common cause of vision loss in the western world. They are either caused by the leakage and neovasculatisation from retinal vessels (diabetic retinopathy, retinal vein occlusions, retinopathy of prematurity and neovascular glaucoma) or by new vessels growing into the retina and subretinal space (AMD, ocular histoplasmosis, pathologic myopia, etc.)
The current treatment options are based on preventing neovasculatisation through using anti-VEGF agents which slow down the progressing disease. New evidence is emerging, however, to suggest that long term use of anti-VEGF agents can have neurotoxic effects. Researchers at UCL Institute of Ophthalmology have identified a new cellular mediator of the angiogenic pathway ABL1 kinase. ABL kinases are druggable targets which can be inhibited providing an alternative treatment to the ani-VEGFs in the management of AMD and ocular neovascularisation.
The Technology and its Advantages
ABL1 protein is involved in a large number of cell signalling pathways and its activity is fine-tuned by various posttranslational modifications and binding proteins. Mutations in ABL1 gene causing abnormal activation of the ABL1 protein are associated with chronic myelogenous leukaemia (CML) and other types of cancer. NRP1 is a non-catalytic receptor for the VEGF165 essential for arteriogenesis, dependent on luminal vessel growth, but dispensable for angiogenesis, driven by vessel sprouting, branching and fusion. The researchers from the UCL Institute of Ophthalmology determined that NRP1-dependent extracellular matrix signalling stimulates cellular migration of endothelial cells and vascular sprout extension and branching by interactions with PXN and via the ABL1 pathway. This data indicates that ALB1 inhibitors available for cancer therapy can inhibit PXN activation and prevent neovascularisation.
According to WHO, AMD is the leading cause of adult vision loss and in 2010 affected over 7.5M people in the seven major markets (US, Japan, France, Germany, Italy, Spain and the UK). Although Wet AMD, which results from the abnormal growth of blood vessels accounts for only 15% of all AMD cases, it is responsible for more than 80% of AMD-related vision loss.
Diabetic retinopathy and macular oedema affect up to 80% of all patients who have had diabetes for 10 years or more and around 10% of all diabetic patients suffers from vision loss related to macular oedema. Diabetic retinopathy is the leading cause of blindness in adults of working age affecting 11.5M people in the seven major markets in 2010. Due to increasing prevalence of diabetes, more people will be suffering from diabetic retinopathy and macular oedema in the future.
Intellectual Property Status
Patent pending, Raimondi et al., 2014.
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