A new drug to treat the muscle wasting disease inclusion body myositis (IBM) reverses key symptoms in mice and is safe and well-tolerated in patients, finds a new study led by the MRC Centre for Neuromuscular Diseases at University College London (UCL) and the University of Kansas Medical Center.

The study, published in Science Translational Medicine, found that the new drug Arimoclomol reversed the disease’s effects at the cellular level and improved muscle strength in mice. A safety trial in 24 IBM patients conducted in London and Kansas found that the drug was safe and well-tolerated.

IBM is the most common muscle disease in people over 45. It is incurable and causes progressive muscle degeneration leading to severe disability, paralysis and dependency. The precise cause is unknown and there are currently no effective treatments.

In this study, the research team pursued a new treatment approach based on observations that muscle tissue from IBM patients contains many misfolded proteins. The research team reported results using an integrated investigational plan of the new drug, Arimoclomol, to clear these proteins out by either refolding or eliminating them.

The team started by creating cells in a petri dish that mimic the muscle tissue of IBM patients, and successfully tested Arimoclomol on these cells. They then used genetically modified mice whose muscle cells and symptoms closely resembled the human disease. An Arimoclomol trial in these mice found that it was well-tolerated, reversed key features of the disease, and importantly, improved muscle strength.

Following a successful patient safety trial, has plans to begin a full-scale randomized controlled clinical trial to formally assess if the drug is effective in slowing disease progression in people with IBM.

Director of the MRC Centre for Neuromuscular Diseases and the UCL Institute of Neurology Professor Michael Hanna, co-senior author of the paper, said: “This is an excellent example of interdisciplinary collaborative translational research that spans discovery, preclinical science and experimental medicine by a group of academic investigators supported by the MRC Centre. Targeting proteostasis has important potential benefit for patients with this disabling degenerative muscle disease. I want to congratulate the entire team and especially the MRC Centre-supported PhD students Mhoriam Ahmed, Pedro Machado, Adrian Miller and Charlotte Spicer. This work was underpinned by our critical collaboration with Linda Greensmith.”

Lead basic scientist and co-senior author Professor Linda Greensmith, Head of the Sobell Department of Motor Neuroscience and Movement Disorders at the UCL Institute of Neurology, said: “Through this collaboration and the support of the MRC Centre we have been able to take our fundamental observations in cell and animal models right through to a proof-of-concept trial in patients. We are actively pursuing this promising approach of manipulation of the heat shock response in IBM as well as other neurodegenerative diseases such as motor neurone disease, in collaboration with the MRC Centre and Danish biotech company Orphazyme ApS.”