Drug candidate to treat muscle spasticity after stroke and nervous system defects

Drug candidate to treat muscle spasticity after stroke and nervous system defects

First-in-class antispastic drug candidate to reach clinical phase is published in the prestigious life science journal, Cell. Drug candidate MPH-220 could mean new hope for millions of patients suffering from spasticity.

Chronic muscle spasticity after nervous system defects like stroke, traumatic brain and spinal cord injury, multiple sclerosis and painful low back pain affect more than 10% of the population, with a socioeconomic cost of about 500 billion USD. Currently, there is no satisfying remedy to help these suffering people, which generates an immense medical need for a new generation antispastic drug.

MPH-220 directly targets and inhibits the effector protein of muscle contraction, potentially by taking one pill per day. By contrast, current treatments have low efficacy and cause a wide range of side effects because they act indirectly, through the nervous system.

"We receive desperate emails from stroke survivors, who suffer from the excruciating symptoms of spasticity, asking if they could participate in our research. We work hard to accelerate the development of MPH-220 to alleviate these people's chronic spasticity" - said the senior author.

The mechanism of action of MPH-220 and preclinical studies are recently published in Cell. The author highlighted: "The scientific challenge was to develop a chemical compound which discriminates between skeletal and cardiac muscle myosins, the motor proteins of these contractile systems. This feature of MPH-220 makes it highly specific and safe."

Mutagenic analysis and the atomic structure of MPH-220-bound skeletal muscle myosin confirmed the mechanism of specificity. Targeting skeletal muscle myosin by MPH-220 enabled muscle relaxation, in human and model systems, without cardiovascular side effects and improved spastic gait disorders after brain injury in a disease model.