Guest blog: Michel Michaelides discusses vital inherited retinal disease research
I was drawn to ophthalmology as a medical student, after taking a period out of clinical training to explore academic ophthalmology. It was clear I had found my niche!
I’m a Consultant Ophthalmologist at Moorfields Eye Hospital in the Departments of Medical Retina, Inherited Eye Disease and Paediatric Ophthalmology; and a Professor of Ophthalmology at the UCL Institute of Ophthalmology.
My research career really began in 2002 when I took time out of clinical training to undertake a two-year period studying the clinical and genetic characteristics of inherited cone disorders, which culminated in a research degree.
My interest in research grew over the rest of my training during my clinical fellowship at Moorfields, and a combined ophthalmic genetics and paediatric ophthalmology clinical and research fellowship at the internationally renowned Casey Eye Institute, at Oregon Health and Science University in the USA.
On returning to the UK, I was awarded a five-year Department of Health/Higher Education Funding Council for England ‘New Blood’ Clinical Senior Lectureship Award and a Career Development Award from the Foundation Fighting Blindness (USA). This allowed me to establish myself as an independent clinician-scientist, form a research team, obtain further funding and publish peer-reviewed articles as a senior author.
My clinical and research interests include diabetic eye disease and inherited eye disease in adults and children. I’m actively involved in retinal clinical trials investigating novel and established therapies, currently being a principal investigator in three on-going gene therapy trials and two pharmacological trials.
My achromatopsia research
I first heard about Fight for Sight thanks to their small grant awards programme.
This grant helped to start our achromatopsia detailed phenotyping and genotyping programme (a condition presenting from birth and characterised by nystagmus (wobbly eyes), marked photophobia (light sensitivity), poor central vision (6/60), and a partial or total absence of colour vision). This grant was invaluable in allowing us to start the CNGB3-achromatopsia gene therapy trial. The molecular basis of achromatopsia has been identified in a large cohort of patients who will potentially be eligible for enrolment into treatment trials. Faults in the CNGB3 gene are one of the commonest genetic causes of achromatopsia. CNGA3 is the second commonest gene associated with achromatopsia – with the phenotyping programme also allowing us to prepare for a CNGA3 gene therapy trial later this year.
We’ve been able to describe the retinal structure of patients with achromatopsia in exquisite detail. These findings will assist in identifying the window of opportunity and the patients who might be most likely to potentially benefit for gene therapy.
My retinitis pigmentosa (RP) research
My current Fight for Sight project grant has allowed me to expand one of the main areas of my research – namely deep phenotyping – characterising structural and functional aspects of inherited retinal disease in detail, to inform clinical trial design and help to provide better information on prognosis.
Cellular imaging is arguably the most exciting structural development in the work we undertake. This is central to the deep phenotyping study funded by Fight for Sight for X-linked RP (XLRP) associated with the gene RPGR.
There is currently no cure for RP, but of the multiple avenues of research being explored, arguably the most advanced is gene therapy.
However, there is a limiting lack of robust natural history data in large genetically proven groups of patients with XLRP due to RPGR mutation. This data is needed so we can design clinical trials for gene replacement therapy and also to provide more informed information on prognosis. We are addressing this lack of data by undertaking a detailed clinical study with serial assessments of genetically proven patients.
The aims of this study include:
- identifying patients who may be most suitable for therapeutic intervention
- establishing the natural history and rates of progression of the condition
- identifying the best time to intervene
- determining the most sensitive and accurate measures of treatment effect
These aims will be achieved by using cutting-edge technology, only available at UCL Institute of Ophthalmology / Moorfields Eye Hospital, to undertake retinal assessments including adaptive optics imaging (allowing the direct visualisation of individual cone and rod photoreceptors in the living human retina) and advanced analysis of retinal sensitivity measurements. This in-depth clinical study is a prerequisite to treatment trials being initiated.
One hundred adults and children with genetically proven RPGR-associated XLRP have been recruited and this investigation should lead to more accurate advice on prognosis and assist genetic counselling. It has resulted in invaluable data about this condition in a large well characterised cohort of patients who have now started to be recruited to our ongoing gene therapy trial for RPGR-associated XLRP.
I’ve been extermely fortunate throughout my career to receive funding for my projects.This funding has enabled me to carry out important research and has allowed me to be involved in clinical trials. I look forward to continuing my research and ultimately improving the lives of patients.
The impact of our work has allowed us to commence three gene therapy trials. We hope that our work will lead to further clinical trials for inherited retinal diseases.