Tackling blindness through gene therapy

Professor Robert MacLaren

An estimated 75 million people worldwide suffer from inherited retinal diseases for which there is currently no adequate treatment.

Such diseases are the leading cause of visual impairment in children in the UK, and of blindness in working-age adults. The early onset of disease impacts the quality of life of those affected and brings significant cost for the health system and wider economy.

‘Most inherited forms of blindness are due to genetic diseases caused by faulty genes in the cells of the retina,’ explains Professor MacLaren. ‘This leads to visual impairment and eventually to blindness.’ Until recently, inherited eye diseases had been considered incurable but new gene therapy techniques developed by MacLaren and his research group may have the potential to slow or even stop retinal degeneration. 

The technique – which involves using a virus to put modified copies of the affected gene back into the cells of the retina to help them to function normally again – was first developed in 2009 to treat choroideremia and subsequently retinitis pigmentosa, which primarily affect young men. Sight loss from these diseases usually begins with ‘night blindness’ in adolescence, followed by a gradual loss of peripheral vision, leading ultimately to blindness.

Eye diseases are well-suited to gene therapy and the approach has huge potential to revolutionise future treatment. The slow rate of cell degeneration offers a long window in which affected cells may be repaired. The small tissue volume of the eye, ease of access it allows for surgery, and the ability to test improved function after treatment are also helpful.

Promising results from initial in vitro research led to the first clinical trials in 2011. Positive outcomes in those led to the spin-out of new gene therapy company ‘Nightstar’ in 2014. ‘Establishing a commercial company allowed us access to new resources and expertise to help develop and evaluate the technique and manage the complex requirements regulating clinical trials and the development of new approved therapies,’ explains MacLaren.

Nightstar and MacLaren’s group have continued to develop gene therapies for choroideremia and retinitis pigmentosa as well as running four other gene therapy research programmes. The former therapies been evaluated and refined in a number of international trials and studies, which have demonstrated that the effects of gene therapy could be sustained over many years. Two innovations are currently awaiting regulatory approval for use in treatment.

Recognising the huge potential of gene therapy to tackle retinal disease, Nightstar was acquired by Biogen for US$877 million in 2019, generating more than £20 million for the University and ensuring a continued income stream as products are licensed. It is now the largest dedicated retinal gene therapy company in the world.

‘Visual impairment caused by genetic disease has a huge impact on the health, well-being and life chances of younger people,’ says MacLaren. ‘Genetic therapy has the potential to transform outcomes for those affected, reduce treatment costs, and extend working lives.’

‘It’s a huge privilege to be able to continue to work as a clinician within an academic context which supports the translation of lab research into commercial development of therapies and I’m very excited about the potential of our work to prevent early visual impairment in future.’

Robert MacLaren is Professor of Ophthalmology in the Nuffield Department of Clinical Neurosciences, Consultant Vitreoretinal Surgeon, and a Fellow of Merton College

Funders:

• National Institute for Health Research
• Wellcome Trust
• Medical Research Council
• Nightstar Therapeutics
• Fight for Sight
• The Royal College of Surgeons of Edinburgh