Enzyme Seen to Reduce Muscle Stiffness Without Side Effects in Small Study

An enzyme called hyaluronidase might reduce muscle stiffness in people with cerebral palsy and other neurological injuries, without causing the muscles to become weak — a major drawback of current approaches to treating muscle stiffness.

The study, “Human Recombinant Hyaluronidase Injections For Upper Limb Muscle Stiffness in Individuals With Cerebral Injury: A Case Series,” published in the journal EBioMedicine, showed that one single treatment with the enzyme significantly reduced stiffness and improved movement ability for three months.

Neurological injury, such as that seen in people with cerebral palsy, often gives rise to muscle spasms. Spastic muscles often turn stiff and rigid, becoming a large contributor to disability in patients.

Researchers still do not understand the molecular events driving the progression of stiffness, or the factors contributing to it.

Preeti Raghavan, MD, lead author of the study, an assistant professor in the Department of Rehabilitation Medicine and director of Motor Recovery Research at Rusk Rehabilitation at NYU Langone Medical Center, together with her team, suggested that stiffness is caused by a molecule called hyaluronan.

Hyaluronan, which is a type of sugar, is used as a lubricant in healthy muscles and joints, allowing muscle fibers to glide smoothly against each other during movement. Raghavan believes that once a brain injury prevents mobility, hyaluronan thickens like honey, contributing to the stiffness.

Dr. Preeti Raghavan (Courtesy of NYU Langone Medical Center)

To test the idea, the team recruited 20 patients with neurological injury who had problems with stiffness. All patients, who ranged from 10 to 77 years of age, experienced moderate to severe stiffness in their arms, and had tried all available treatments without success.

The patients received injections of hyaluronidase — an enzyme that breaks down the hyaluronan molecule — in the affected muscles. Patients were filmed before and, on three occasions, after the injections. Their medical records were also analyzed.

Patients were tested for stiffness before receiving the injections, and 50.6 percent of all their joints showed moderate stiffness and 44.4 percent severe stiffness. At the first assessment, performed two weeks after the injections, those numbers had dropped to 15.3 percent with moderate stiffness and 5.8 percent with severe stiffness.

Further tests, performed at four to six weeks and at three to five months after the injections, showed that the treatment produced its full effect within two weeks, lasting for at least three months. Importantly, the treatment mainly gave rise to mild side effects linked to the injection. No patient had any serious side effect.

“These findings fill a critical gap in the understanding of muscle stiffness, and present a promising treatment for spasticity, a vexing problem that affects millions of people worldwide,” said Raghavan in a news release.

The cost of one treatment ranged from $200-$400, which is considerably lower than the price of Botulinum toxin injections (at least $2,000), which are commonly used for stiffness in these patients.

Hyaluronidase treatment for muscle spasticity and stiffness is not an approved treatment, but Raghavan plans to conduct a clinical trial, which, among other things, will assess the effects of repeated injections of hyaluronidase.

“This case series provides preliminary evidence for the safety and potential efficacy of hyaluronidase injections as a treatment for muscle stiffness that may enhance recovery in the spastic upper limb. More research may determine whether such a treatment is applicable to other disorders characterized by muscle stiffness,” Raghavan said.

NYU Langone has filed a patent for hyaluronidase for muscle stiffness.