Reduce blindness due to conditions of singular genetic eye diseases, by developing a greater understanding of genetic causes of eye disease, and the creation of novel treatments and therapies.
Most chronic diseases are strongly influenced by many gene variations, leading to a ‘polygenetic’ influence on disease likelihood. Single gene disease causes are less common, but occur more frequently in the eye and can devastate vision in childhood, and have a significant impact on families. The most common types – ‘inherited retinal diseases’ (IRDs) and ‘hereditary optic neuropathies’ (HONs) – affect the retina and optic nerves. They are caused by familial genetic mutations, and usually lead to blindness. Although individual types of IRD and HON are rare, collectively they are the most common cause of blindness in the working-age population, affecting 1:2000 people. The most common disease is Retinitis Pigmentosa, affecting 1:4000.
The first single gene therapy using a viral carrier vector for an eye disease was approved by the Food and Drug Administration (FDA) in 2018. Lions Eye Institute scientists were involved in developing this pioneering work, which paves the way for other singular gene repair and genetic protein production therapies. Several chronic diseases such as age-related macular degeneration (ARMD) can be treated by specific receptor blocking proteins, which could potentially be made long-term injecting protein-producing genes.
IRDs and HONs can be debilitating and traumatic for individuals and their families, and it is critical that we develop a greater understanding of these diseases and novel therapies to treat them. This requires a four-pronged approach: (1) a comprehensive natural history study, (2) a tissue and DNA bio-bank for biomarker and DNA analysis, (3) laboratory discovery of new pathways and treatments through animal and cell models, and (4) bench to patient translation through clinical trials.
Our work, our achievements
The most common purely genetic eye diseases are those that affect the retina and optic nerves. The key to understanding who, when and how IRDs, HONs and ARMD should be treated is detailed clinical information about the natural history of these conditions.
- The Lions Eye Institute is the only centre in Australia that has an active natural history study in IRDs, HONs and ARMD. We have one of the most comprehensive clinical image banks of these conditions, which will provide answers to the key questions today: which patients with early stage disease will progress? How fast will the cell death progress? When is the best time to intervene?
- To understand these diseases at a cellular level, we have collected and banked human tissue from several hundred patients with IRDs, HONs and ARMD with detailed clinical assessment.
- The Lions Eye Institute is the host for the Australian IRDs and HONs DNA Bio-Bank, a genetic library containing material from over 7,000 patients and their family members across Australia. The tissue and DNA bank is the largest of its kind in Australia. Although almost 1000 patients’ DNA has been analysed, many more are not yet examined. There are biomarkers in ARMD patients’ blood which have prognostic and diagnostic value.
- We are at the forefront of the development and validation of cell models of IRDs and HONs, to better understand the disease mechanism and test novel drugs and gene therapies to prevent blindness. These new drugs have led to patents and the formation of spin-off companies (e.g. Vision Pharma: PYC Therapeutics), providing a platform for pre-clinical testing and clinical trials of other genetic targets of drug therapy.
- Within the growing ocular gene therapy field, we are at the forefront, leading the research into developing a gene therapy-based treatment that could allow the eye to continuously produce the necessary drug to treat the wet form of ARMD. The phase 1 trial for this gene therapy was conducted at the Lions Eye Institute.
- Real translation of laboratory discovery cannot occur without clinical trials. We have a long track record of conducting retinal disease drug trials and we currently have several active trials involving IRDs and ARMD.
