Sheffield Institute for
Translational Neuroscience

Therapy Development

1. Gene therapy programme

Professor Mimoun Azzouz, previously Head of Neurobiology at Oxford Biomedica, is one of the leading experts in the UK in the use of gene therapy for neurodegenerative diseases. He leads an extensive programme at SITraN aiming to replace or silence faulty genes in forms of MND which are caused by a known gene mutation such as SOD1 and C9orf72.

Professor Azzouz has already proven and published the concept that switching off the expression of the mutant SOD1 gene that causes MND in mice extends survival by 80% and delays the onset of symptoms by over 100%. To silence the mutant SOD1 gene, the team uses inhibitory RNAs (RNAi) which are introduced into the cell using a virus-like carrier called adeno-associated virus (AAV9).

The SITraN team hopes to take the SOD1 gene therapy forward to clinical trials in the UK in the near future and develop similar approaches for other genetic variants of MND. Further promising new gene targets identified in our cellular models will be taken forward into in vivo studies in mice.


Prof Mimoun Azzouz

2. Pre-clinical drug screening programme and drug re-purposing strategy

SITraN has invested in a state-of-the-art drug screening facility. We evaluate all our candidate therapies in a hierarchical cascade of in vitro and in vivo models – cell culture, zebrafish and mice - and correlate our findings back to human samples.

We test potential drugs, partly in collaboration with industry partners, and large libraries of compounds which have already proven safe to treat other diseases in humans. If these drugs show neuroprotective benefits in MND, they can be repositioned and fast-tracked into clinical trials, saving decades of research and millions of pounds. Our current discovery pipeline includes drugs which have effects on oxidative stress, axonal transport and inflammatory mechanisms.

Dr Richard Mead, supported by the MND Association and Mr Nicholas Snowman, brought his extensive experience of working with mouse models of neurological disease from Cell Tech Cambridge to SITraN and leads an extensive pre-clinical drug screening programme in mice.

We have developed standardised markers to carefully define onset and progression of the disease in mice. Through pre-clinical pharmacokinetic analyses in collaboration with colleagues in  Analytical Chemistry at the University of Sheffield, we have optimised methods of drug delivery to achieve optimal dosing and good penetration through the blood-brain-barrier.


Drug Screening



Handling drug libraries