Autosomal dominant optic atrophy (ADOA) is the most common inherited optic neuropathy, with an incidence of 1:12-15,000.  It is caused by mutations in a gene called OPA1, which causes the power-house in each cell, the mitochondria, to lose normal function.  The mitochondria in ADOA patients do not generate sufficient energy and they produce toxins.

Cells in the eye which take the information from the eye to the brain through the optic nerve, called retinal ganglion cells (RGCs), are particularly susceptible to dame caused by loss of proper mitochondrial function.  This is what happens in ADOA and the RGCs become sick and die, which then leads to blindness.  Currently there is no treatment for ADOA.  the condition affects predominantly young people and is slowly progressive.  The upshot is a long-lasting, debilitating lifelong problem, severely impacting on quality of life and the ability of full independence.

The aim of this project is to develop a novel treatment to correct the mitochondrial function in patients with ADOA and thereby to prevent blindness or arrest its progression.

To achieve this aim, we will use discoveries from our recent work, in which we designed new drugs, and tested them on isolated mitochondria and cultured cells. Now we have reached a stage where the efficacy of the four most promising of these drugs need to be verified.

Firstly we will access the RGC damage responsibility for blindness by looking at how the RGCs lose their branch structures, which are responsible for gathering visual information.  Secondly we will test the new drugs for loss of structure.  Thirdly, data from these experiments will inform further optimisation of the chemical structures of the four drugs to make them work even better.  Lastly, we will explore a range of novel advanced drug delivery strategies to target the rear of the eye in order to achieve the maximum therapeutic effect, which has an exciting potential to lead to new treatments.

The result of this study was that Prof Marcela Votruba and her team identified the most appropriate drug candidate and formulation. Further research is now being done, to identify how to deliver these drugs which could be used eventually in clinical trials.