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.
The study led by the MRC Centre for Neuromuscular Diseases at University College London (UCL) and the University of Kansas Medical Center 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 the study, the research team pursued a new treatment approach based on observations that muscle tissue from IBM patients contains many misfolded proteins. 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, there are 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.
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: “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.”