Monoclonal xIL-6R antibodies as a treatment for memory dysfunction in the mdx mouse model of Duchenne muscular dystrophy

Duchenne Muscular Dystrophy (DMD) is a genetic disorder that affects ~ 1 in every 3,600 live male births. This disease is characterised by progressive muscle weakness, disability, immobility and premature death, often due to respiratory failure. Symptom manifestation is due to a genetic mutation in the dystrophin gene, which protects skeletal muscle cells from damage caused by contraction. Loss of dystrophin leads to loss of muscle function and chronic inflammation, with elevated levels of immune signalling molecules such as interleukins (IL).



Although no cure is available for this devastating disease, recent advances in care have led to prolonged lifespans and interest in non-muscle related aspects of the disease has gained momentum. Boys with DMD often have lower intelligence quotients and deficits in verbal memory. Moreover, the genetically comparable mdx mouse model of DMD also exhibits poor memory consolidation and neuronal loss in brain regions linked to learning and memory formation. However, the mechanisms underlying these deficits isn't clear and therapeutic strategies remain elusive.



The aim of the proposed programme of research is to investigate a potential therapeutic intervention to improve cognitive dysfunction related to dystrophin deficiency. Linked to chronic inflammation, levels of pro-inflammatory immune molecules such as IL-6 are elevated in DMD and mdx mice. IL-6 is known to modulate neuronal function. Thus, we will use the pre-clinical mdx mouse model of DMD to assess the potential role of IL-6 in memory formation in mdx mice. Electrophysiological techniques will be used to assess if treatment normalises aberrant neural signalling in the brain. These studies may reveal a novel therapeutic target for improving the quality of life of DMD sufferers.

Award Date
30 June 2017
Award Value
€158,285
Principal Investigator
Dr Dervla O'Malley
Host Institution
University College Cork
Scheme
Investigator Led Projects