Investigating the pathogenetic mechanisms leading to progressive scarring and glaucoma surgery failure and development of new targeted therapeutics

点击翻译按钮获取中文摘要

Glaucoma is a major health problem and blinds millions of people worldwide. Glaucoma surgery is used to prevent blindness, but it fails primarily due to scarring in 50% of patients after 5 years of follow-up. The James Lind Alliance and the Sight Loss and Vision Priority Setting Partnership list among the top priorities for glaucoma research the detection of glaucoma patients with a higher risk to progress rapidly and the improvement of treatments for glaucoma. I will use new powerful technologies to investigate why a large subgroup of patients develops severe scarring and irreversible loss of vision after glaucoma surgery. Using this knowledge, I will develop new treatments to prevent this from happening.KEY GOALS:1) To prospectively study 300 patients after their first glaucoma surgery in detail over 18 months to identify the complex factors that cause scarring, and to look for markers that predict a high risk of scarring and surgical failure.This research will use cutting-edge techniques on eye tissues and detailed eye examination from patients to study the complex factors associated with scarring after glaucoma surgery. This project will directly improve the management of glaucoma patients by identifying the high-risk patients who are more likely to fail surgery and who need additional treatment to prevent surgical failure.2) To develop new treatments to target the key factors that cause scarring and to prevent glaucoma surgery from failing.The current gold standard, mitomycin-C, is a non-specific toxic anti-cancer drug with blinding side effects. There is thus a large unmet clinical need for new drugs with more targeted effects and less toxicity. I will develop new targeted drugs to silence the key factors that lead to scarring after glaucoma surgery. I will also test the most effective targeted drugs using a rabbit model of glaucoma surgery. These studies will help to inform future clinical trials of targeted drugs in glaucoma.This project's ultimate aim is to develop and translate a new anti-scarring drug to increase the success rate of glaucoma surgery, without exposing patients to the risk of toxic anti-cancer drugs. I will form industrial partnerships to target the key factors that cause scarring and for the translation of new targeted drugs in glaucoma patients. I will also work with the Good Manufacturing Practice (GMP) facility at the Rayne Institute (King's College London) to develop a safe and consistent method to manufacture the new targeted drugs, which can be tested in glaucoma patients in future clinical trials.BENEFITS:This Fellowship is innovative and brings together the expertise of multiple academic disciplines and fields (clinical doctors, academic leaders in molecular genetics and targeted drugs, key industrial partner in drug development, GMP facility partner in gene therapy). This project will directly improve the management of glaucoma patients by identifying those who are more likely to fail surgery, and by developing new targeted and personalised treatments.