Inclusion Body Myositis (IBM)

Mhoriam Ahmed

Led by Dr Mhoriam Ahmed

Sporadic Inclusion body myositis (IBM), the commonest acquired muscle disease affecting people over 50 years old, is characterised by progressive muscle weakness and atrophy in specific muscles including key muscles in the arms (forearm flexors) and the legs (quadriceps), resulting in severe disability. Although IBM aetiology involves both muscle fibre degeneration and chronic inflammation, previous clinical trials have targeted only the inflammatory component of IBM and all were ineffective. IBM therefore remains without treatment.

Muscle biopsies from IBM patients show the presence of myofibres of irregular size and shape, atrophied and necrotic fibres and a significant level of inflammation around the fibres. In addition muscle fibres characteristically contain inclusion bodies which are large aggregates of abnormal proteins within the fibres themselves. The presence of these abnormal proteins suggests that the crucial balance of proteins in the muscle cell (the protein homeostasis) may be disrupted. Maintaining a healthy protein homeostasis is fundamental in all cell types. Therefore an imbalance may play a role in disease pathogenesis, causing the muscle damage seen in IBM patients. Addressing the presence of abnormal proteins is therefore a rational target for a potential treatment for IBM. This has been one focus of our research on IBM.

As part of a collaboration with Professor Mike Hanna, we have taken a translational approach to our research in IBM, where findings from the lab are directly channelled towards benefiting patients. To this end, we have established and characterised preclinical models of IBM, both cell based as well as animal models, which can be used to investigate the underlying pathophysiology of the IBM and to assess the effects of novel therapeutic agents.

We have developed robust culture models of IBM, in which muscle cells develop IBM-like pathological characteristics which can be assessed for drug testing studies. These features were induced either by over-expression of an IBM-relevant protein or by exposure to pro-inflammatory molecules, thus modelling two major aspects of the disease. These models have been instrumental in identifying novel drugs to take forward into animal studies of IBM.

Based on our results from the cell culture model of IBM, we are currently examining the efficacy of a novel potential therapeutic compound in vivo in a mouse model of a hereditary form of IBM.

In parallel, Professor Hanna and his colleagues have just completed a safety and tolerability trial of this compound in patients with IBM.

Page last modified on 01 apr 14 14:19