Around two million people live with sight loss in the UK (1). With more than one million blind and partially sighted people living with sight loss caused by a long-term eye health condition that cannot be reversed, such as age related macular degeneration, glaucoma, and diabetic eye disease.
Until recently, some eye diseases had been considered incurable but new gene therapy techniques have shown great promise. However, increasing evidence from clinical trials have reported problems with unexpected eye inflammation, leading to vision loss in some patients.
Inflammation is a major challenge for this type of treatment because it can limit its effectiveness. Researchers at Bristol wanted to better understand how the eye reacts to the methods used to deliver the therapy, not the disease itself, to improve safety and effectiveness of future treatments.
In gene therapy techniques, a harmless virus called the Adeno-Associated Virus (AAV) is modified to deliver the therapeutic genes into cells at the back of the eye helping them to function normally again and preventing disease. This delivery system is widely used in gene therapy because it can efficiently enter cells and deliver the genetic instructions needed to treat disorders, such as those which can lead to sight loss and blindness.
Scientists believe some of the adverse side effects from AAV gene therapy are caused by the immune system recognising the delivery virus as potentially harmful. This impacts the effectiveness of gene therapy either directly through inflammation or indirectly as it limits necessary dose increases.
To improve the safety and effectiveness of these gene therapies the researchers wanted to better understand these responses so they can develop management strategies.
Read the full University of Bristol News item
Paper: ‘Characterisation of the ocular inflammatory response to AAV reveals divergence by sex and age’ by Alison J. Clare, Philip M. Langer, Amy Ward, Ying Kai Chan, Andrew D. Dick, David A. Copland in Molecular Therapy [open access]