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A Therapy For Wet AMD And Other Conditions Where There Is Abnormal Blood Vessel Growth
Researchers at Moorfields Eye Hospital and UCL Institute of Ophthalmology have discovered a new molecule called leucine-rich alpha-2-glycoprotein 1 (LRG1) which could hold the key for future therapy of a number of conditions where there is abnormal blood vessel growth, including age-related macular degeneration (AMD), rheumatoid arthritis, proliferative diabetic retinopathy, atherosclerosis and cancer. The research team has now received £5.6 million funding from the Medical Research Council (MRC) to conduct early phase clinical trials.
Why the LRG1 Trial?
Angiogenesis – the growth of blood vessels - is essential for normal development and tissue repair but uncontrolled vessel growth can also be harmful when, for example, it supports the growth of solid tumours or when the vessels that form are abnormal and leaky as in the ‘wet’ form of AMD. Therefore, blocking the activity of LRG1 to prevent the uncontrolled growth or formation of abnormal vessels in these circumstances might help to prevent disease progression.
The researchers discovered that in conditions like wet AMD, LRG1 activity is ‘switched on’ and this encourages another molecule called transforming growth factor beta (TGF-beta), to shift from maintaining normal, healthy blood vessels towards promoting growth of new disorganized blood vessels. These abnormal blood vessels have a tendency to be thin walled and leaky which can result in fluid and blood leaking into the eye killing-off cells in the region of the eye called the macular which causes damage to peoples central vision.
To block the activity of LRG1 the research team has employed the immune system to generate an antibody, a process that is normally used by the body to seek out and destroy ‘foreign’ material, like bacteria and parasites, that might cause illness. The antibody, called Magacizumab, specifically recognises LRG1 and blocks its biological activity which prevents it from causing a switch in the activity of TGF-beta. This results in a decrease in the growth of these dysfunctional blood vessels.
A study published in Nature showed that, in the laboratory, this novel therapy was effective in homing in on LRG1 and stopping abnormal blood vessels from forming (Wang, 2013).
The two research scientists leading on the LRG1 trial are Professor Stephen Moss and Professor John Greenwood. The clinicians carrying out and coordinating the trial will be Professor Adnan Tufail and Professor James Bainbridge.
Reference
1. Wang X, Abraham S, McKenzie JA, Jeffs N et al. LRG1 promotes angiogenesis by modulating endothelial TGF-β Nature 2013 ;499(7458):306-11
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