Completed

June 2013 - June 2016

Developing a blood test to predict the risk and course of AMD

Research Details

  • Type of funding: Project Grant
  • Grant Holder: Grant holder Dr Claire Harris
  • Region: Wales
  • Institute: Cardiff University

Overview

Age-related macular degeneration (AMD) used to be thought of as an unavoidable part of ageing. But it turns out to be driven by long-term low levels of inflammation. This means a change in thinking about how to treat it.

Inflammation happens when parts of the body’s immune system are activated in the wrong place, are over-activated or stay active for too long. One part of the immune system that’s important for driving inflammation is a set of proteins called ‘complement’ proteins.

Complement proteins normally work together to kill bacteria and other invaders. They switch on inflammation as a signal that tells immune system cells where to go to eat the attackers.

When the invasion has been dealt with, complement proteins and inflammation usually stop being active. But there’s evidence that they continue in AMD. And people with particular variations in complement system genes are more (or less) at risk of getting AMD.

There are tests that can tell people which variations they have in complement genes. But it’s not clear exactly what the results mean in terms of predicting the risk of AMD, how it will develop and how people might respond to treatment.

In this project the team is aiming to develop a blood test that can give a better idea of who is at risk of AMD. The results should also help to predict how people will respond to current or new treatments as they are developed.

  • Scientific summary

    The complotype as a predictor of disease and response to therapy in AMD.

    Complement was first implicated in age-related macular degeneration (AMD) around the turn of the century when immunohistological studies showed complement proteins, regulators and activation products were abundant in drusen. Interest exploded in 2005 with the demonstration that polymorphism in the complement regulator factor H was a powerful predictor of disease risk. Since then, over 400 publications have appeared linking complement and AMD.

    Despite this enormous activity, it remains unclear precisely how complement contributes to initiation and propagation of retinal damage in AMD, and uncertain whether complement proteins are useful markers of disease susceptibility, severity, progression rate or response to therapy. Dr Harris and team are addressing this gap by developing multiplexed assay sets selected for utility in AMD that measure serum levels of relevant complement proteins, polymorphisms and activation products selected based upon literature evidence and their preliminary work.

    The assay sets, measuring the patient AMD-relevant complotype, are being optimised and applied to patient and control cohorts to test the diagnostic value of the individual analytes. The power and predictive value of the assay set, after correction for known confounders, are being measured and compared to individual component assays and genetic screening. The assay sets are being used in AMD patients beginning anti-VEGF therapy and the relationship of the patient complotype to response to therapy is being assessed. At the end of this project the team will be in a strong position to replicate their findings in other large, well-characterised AMD cohorts to confirm the influence of the complotype on disease course and treatment. Information gained will aid diagnosis and dictate treatment choice.