Identifying novel therapies for inherited eye disease
Scientists are working to define the mechanisms leading to cell death in inherited eye conditions to help develop targeted treatment options and prevent sight loss.
Mutations in over 280 genes lead to death of the light-sensing photoreceptor cells at the back of the eye, causing untreatable blindness in many.
While gene therapy has brought the field hope, genes must be targeted one at a time which means it could take many years for this technology to be developed for the rarer conditions.
Dr Roly Megaw’s research at the University of Edinburgh aims to address the need for treatments that are effective for many inherited retinal dystrophies (IRDs), regardless of genetic causes.
The study could be incredibly important for patients affected by genetic eye conditions and their families, for clinicians who care for these patients, and the UK taxpayer in general.
The how
The research will determine if our light sensing photoreceptors die by the same mechanism in inherited retinal dystrophies, regardless of the gene involved. If so, targeting the pathway could help in a gene-independent manner.
The research will primarily focus on autophagy, the body's way of clearing out damaged cell debris, and recycling cell components in order to keep them healthy.
The team will assess the disruption of this process (otherwise called autophagy flux, due to the passing or travelling through of cells) and the molecular networks that become unregulated in stressed and dying photoreceptors.
The team will also investigate the capacity of cell death inhibitors to prevent the degradation of photoreceptor cells and improve retinal function.
By doing so, they aim to identify therapeutic targets that can be brought forward for drug delivery studies and eventually clinical trials.
Speaking about the project, Dr Megaw told us:
“If we are able to identify the cell death pathway responsible for photoreceptor loss in inherited eye diseases, and identify a drug to stop this no matter the gene involved, it could point towards a novel treatment for inherited eye disease.”
The why
IRDs are the leading cause of visual loss in children and adults of working age. In 2019 alone they cost £523.3m in economic and well-being costs in the UK.
At present there is only one gene therapy treatment available for a very rare form of IRD and trials to date show the visual improvement is modest. Although there are more targeted gene therapies in trial, there is still a need for complementary therapies to prevent photoreceptor death that can be used in combination with gene therapy, and in rarer forms of disease where the specific gene has not been targeted.