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The role of the gene SERPINH1 as a pharmacogenetic biomarker for choroidal neovascularization (CNV) responses to anti vascular endothelial growth factor (VEGF) treatment in clinical practice

The role of the gene SERPINH1 as a pharmacogenetic biomarker for choroidal neovascularization (CNV) responses to anti vascular endothelial growth factor (VEGF) treatment in clinical practice
The role of the gene SERPINH1 as a pharmacogenetic biomarker for choroidal neovascularization (CNV) responses to anti vascular endothelial growth factor (VEGF) treatment in clinical practice
Age related macular degeneration is the commonest cause of blindness in the western world and current treatment regimens represent a significant output for national health services. The disease process is multifactorial in origin and has a variable progression and response to current methods of treatment. A targeted approach with individualized therapy based on recognized biomarkers to predict disease outcome would be the ideal treatment modality.

We plan to investigate the role of genes known to influence the progression of early AMD to the advanced stage (wet AMD) with emphasis on genes involved in complement regulation (SERPING1, CFB, CFI, CFH, C2 and C3). The investigation will also encompass other genotypes involved in AMD pathogenesis.

Polymorphic variations in the gene SERPING1, which codes for complement 1 inhibitor (C1Inh), have been previously implicated in AMD pathogenesis. Many clinical trials involving complement antagonists are currently proceeding at various stages of development. We plan to investigate the role of C1Inh in AMD development and explore its potential as a therapeutic agent, utilising Ccl2-/-/Cx3cr1-/- (in the presence of an rd8 mutation in the Crb1 gene) and wild type C57BL/6 mice. In the neurodegenerative condition Alzheimer’s disease, acute or chronic and chronic systemic inflammation have been associated with progression of symptoms. Both chronic and acute inflammation have been implicated in choroidal angiogenesis and subsequent AMD development. We hypothesised that systemic inflammation may alter the response of AMD to the anti-vascular endothelial growth factor (VEGF) agent ranibizumab. Inflammatory markers may therefore offer an objective indicator of future treatment response. These experiments will provide a comprehensive analysis of prognostic indicators for AMD and investigate a potentially new therapeutic agent.
University of Southampton
Pierce, Charles
5705c4e1-86f6-49cb-80e7-9f58903d69f4
Pierce, Charles
5705c4e1-86f6-49cb-80e7-9f58903d69f4
Lotery, Andrew
5ecc2d2d-d0b4-468f-ad2c-df7156f8e514

Pierce, Charles (2015) The role of the gene SERPINH1 as a pharmacogenetic biomarker for choroidal neovascularization (CNV) responses to anti vascular endothelial growth factor (VEGF) treatment in clinical practice. University of Southampton, Doctoral Thesis, 313pp.

Record type: Thesis (Doctoral)

Abstract

Age related macular degeneration is the commonest cause of blindness in the western world and current treatment regimens represent a significant output for national health services. The disease process is multifactorial in origin and has a variable progression and response to current methods of treatment. A targeted approach with individualized therapy based on recognized biomarkers to predict disease outcome would be the ideal treatment modality.

We plan to investigate the role of genes known to influence the progression of early AMD to the advanced stage (wet AMD) with emphasis on genes involved in complement regulation (SERPING1, CFB, CFI, CFH, C2 and C3). The investigation will also encompass other genotypes involved in AMD pathogenesis.

Polymorphic variations in the gene SERPING1, which codes for complement 1 inhibitor (C1Inh), have been previously implicated in AMD pathogenesis. Many clinical trials involving complement antagonists are currently proceeding at various stages of development. We plan to investigate the role of C1Inh in AMD development and explore its potential as a therapeutic agent, utilising Ccl2-/-/Cx3cr1-/- (in the presence of an rd8 mutation in the Crb1 gene) and wild type C57BL/6 mice. In the neurodegenerative condition Alzheimer’s disease, acute or chronic and chronic systemic inflammation have been associated with progression of symptoms. Both chronic and acute inflammation have been implicated in choroidal angiogenesis and subsequent AMD development. We hypothesised that systemic inflammation may alter the response of AMD to the anti-vascular endothelial growth factor (VEGF) agent ranibizumab. Inflammatory markers may therefore offer an objective indicator of future treatment response. These experiments will provide a comprehensive analysis of prognostic indicators for AMD and investigate a potentially new therapeutic agent.

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Thesis FINAL C Pierce Jun 2015 - Version of Record
Available under License University of Southampton Thesis Licence.
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Published date: April 2015

Identifiers

Local EPrints ID: 417281
URI: http://eprints.soton.ac.uk/id/eprint/417281
PURE UUID: 20dab593-9ce6-4a7b-9371-5c7bdf5a4b8f
ORCID for Andrew Lotery: ORCID iD orcid.org/0000-0001-5541-4305

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Date deposited: 26 Jan 2018 17:30
Last modified: 14 Mar 2019 01:44

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