Mitochondrial optic neuropathies are an important group of disorders that affect at least 1 in 10,000 individuals in the UK. They are characterised by the malfunction of mitochondria, small organelles present in our cells.

Mitochondria are fundamental components for cells; they can convert the food we eat into energy, playing a key role in their life and death. In particular, in this group of disorders, the mitochondrial dysfunction leads to progressive blindness. Unfortunately, to date, these diseases are currently incurable. Hence, there is a pressing need to identify novel treatments.

Professor Marcela Votruba at Cardiff University, along with her team, are aiming to develop sustained release formulations for new drugs in the treatment of mitochondrial optic neuropathies.

The two most common mitochondria optic neuropathies are Leber Hereditary Optic Neuropathy (LHON) and Autosomal-Dominant Optic Atrophy (ADOA). ADOA and LHON are caused by mutations associated with our genes. These mutations lead to a harmful change in the mitochondria which lose their normal function.

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 damage caused by loss of proper mitochondrial function. Mitochondrial optic neuropathies lead to life-long, debilitating loss of vision, severely impacting on quality of life and independence.

In previous work undertaken by Professor Votruba, also funded by NERC, the team designed new drugs, and tested them on isolated mitochondria and cultured cells and retinas. These new drugs can restore the mitochondria energy in cells, resulting in the rescue of cell death. The results obtained in their work are promising, and now they wish to convert them into a usable medicine.

Firstly, they will isolate sufficient amounts of the four compounds and then develop an effective ocular drug delivery system. Then determine the ability of the drugs to penetrate into pig eyes. Lastly, they will evaluate their ability to get the drugs into the eye of a mouse with a mitochondrial defect and see if they appear to prevent retinal ganglion cell loss.

The expected outcome of this work is the identification of the most appropriate drug candidate and formulation, which could be used eventually in clinical trials in patients with LHON or ADOA.

This project has been disrupted by laboratory closures during COVID-19 lockdown measures and it will require further time and funding to reach its successful completion. Please give today, if you can.