EYE-D: Therapeutic target identification for degenerative retinal disease
What is EYE-D?
Over 224,000 Irish people and 40 million people worldwide are affected by severe vision loss. This number of people continues to increase, largely due to our ageing population. Up to 80% of all eye diseases worldwide are preventable, however, patients continue to lose their sight due to the limited drugs currently on the market. One key reason for a lack of efficient drugs is that the underlying molecular causes of these conditions are still not fully understood.
EYE-D, launched in October 2021 and funded under the Research Ireland Strategic Partnership Programme[KA1] , brings together a consortium of leading university experts from Trinity College Dublin (TCD), industry partners (Roche and Disarm/Eli Lilly), a private eye clinic (Progressive Vision Research) and a patient-led charity (Fighting Blindness Ireland), with the aim of tackling some of the most pressing challenges and needs in the ophthalmic disease space. EYE-D is focused on understanding the root molecular causes of these diseases and to rapidly develop the next generation of therapies.
What are the key research areas in EYE-D?
- Understand the early causative factors that drives age related macular degeneration (AMD) development and identify novel therapeutic targets
- Driving the development of a new form of therapy to treat open-angle glaucoma
- Elucidation of the basic mechanisms of retinal degeneration
Who is involved?
EYE-D is hosted by TCD, with the consortium comprising of four co-funding partners:
- Progressive Vision Research is a private eye clinic based in Dublin and provides clinical and optometry support. The partnership has allowed clinical research to be carried out in a private ophthalmology clinic setting.
Progressive Vision Research are delighted to be involved in the EYE-D project in collaboration with TCD. Patients are the focus of the Progressive Vision Clinic and it is exciting to be able to give them the opportunity to get involved with cutting edge research activities. We look forward to continued collaboration.” Dr Aideen Curtin, CEO, Progressive Vision Research.
- Fighting Blindness Ireland is an Irish, patient-led charity with a vision to cure blindness and support people living with sight loss. The charity funds two projects in the research programme and has allowed for the procurement of a state-of-the-art microscope that has expedited scanning of retinal samples. They also ensure that the results of our research are conveyed in a patient-centric manner to those with sight-threatening diseases.
“The involvement of a patient-led charity partner such as Fighting Blindness Ireland is critical in exposing trainees to the realities and impact their research can have in the real world. It also allows us as researchers to co-design our projects with the patients’ needs front and centre of any research output, whether clinical or pre-clinical.” Prof. Matthew Campbell, academic partner."
“Fighting Blindness Ireland are delighted to be part of the innovative Research Ireland-SPP EYE-D programme. We are excited to support the involvement of patients in ongoing clinical research, bringing us closer to identifying treatments for conditions of sight loss. We look forward to our continued collaboration with the Campbell lab in TCD on this important project.”
- Roche is a global healthcare company, with its ophthalmology arm focused on pioneering therapies to prevent vision loss. They support the EYE-D research programme to understand novel mechanisms behind retinal degeneration in AMD.
“Partnering with TCD through the Research Ireland-SPP programme has given my group the exciting opportunity to partner with CNS vasculature experts to conduct exploratory projects that we hope will identify novel targets and biomarkers. These types of studies will inform future therapies to prevent vision loss in patients with diverse retinopathies.”
- Disarm Therapeutics is a wholly-owned subsidiary of the pharmaceutical company Eli Lilly and Company and is involved in supporting the exploration of neurodegenerative mechanisms by providing their proprietary inhibitors to prevent common pathologies in a range of ocular diseases.
“The Disarm/Eli Lilly-TCD collaboration has been a great partnership in helping Eli Lilly to expand the potential for SARM1 therapeutics. The Doyle lab had published foundational scientific research on the role of SARM1 and its therapeutic potential in both age-related macular degeneration and inherited retinopathy retinitis pigmentosa. This collaboration has enabled Eli Lilly to capitalize on the lab's expertise and translate the lab's earlier findings into a therapeutic strategy by testing SARM1 ASOs in mouse models of retinal degeneration. Over the past year we have met bimonthly to discuss data and assess progress toward the grants objectives. The collaboration has made great progress with high quality data and is on track to accomplish our objectives.”
Research Impact
A novel gene therapy for the treatment of open-angle glaucoma has been developed in collaboration with TCD spinout Exhaura Ltd. as well as the company Virscio. Exhaura has also raised €1M in seed financing in the past 18 months. This company has been able to bring an asset to the stage of an Investigational New Drug (IND) filing with the FDA.
We have found that the inner blood-retina barrier (iBRB) becomes slightly ‘leaky’ as people age. By studying large patient cohorts, we’ve discovered that this leakage happens simply due to aging, not just in those with age-related macular degeneration (AMD) as we previously thought. Interestingly, the daily rhythm of the iBRB’s integrity continues in the central part of the retina in healthy older adults, but not in those with AMD. This central part is the last area to remain intact in the late stages of dry AMD. Treating with Repsox, a drug that regulates a protein called claudin-5, significantly reduced the development of lesions. This is some of the first evidence that controlling claudin-5 levels can help prevent the progression of neovascular eye diseases in animals.
Contact Information:
Prof. Matthew Campbell: campbem2@tcd.ie
Prof. Sarah Doyle: doyles8@tcd.ie
Progressive Vision Research: https://www.progressivevision.ie/
Aideen Curtin, CEO, Progressive Vision Research: aideen@progressivevision.ie
Fighting Blindness: https://www.fightingblindness.ie/
Ellen Moran, Head of Research, Fighting Blindness: ellen.moran@fightingblindness.ie
Roche: https://www.roche.com/innovation/structure/rnd-locations/pharma-basel
Peter Westenskow, Discovery Ophthalmology Lead, Roche: peter.westenskow@roche.com
Eli Lilly/Disarm: www.lilly.ie
Raul Krauss, Vice President, Co-founder and Head of Biology, Eli Lilly/Disarm: krauss_raul@lilly.com