Novel Treatment Method for Restless Legs

Clemens, along with associate professor Kori Brewer, examine a mouse’s spinal column in their lab at the Brody School of Medicine. Clemens’ work with mouse models was essential in helping him develop his Restless Legs Syndrome treatment.

Media Release:

An East Carolina University faculty member’s latest patent may change the way Restless Legs Syndrome (RLS) is treated, leading to more effective care over a longer period of time for patients.

Stefan Clemens, an associate professor in the Brody School of Medicine’s Department of Physiology, was awarded U.S. Patent 10,751,327 on Aug. 25 for his novel treatment method for the treatment of RLS.

Restless Legs Syndrome is a nervous system disorder that affects between 5% and 8% of the population in the United States. Those suffering from RLS experience an uncontrollable urge to move their legs caused by an unpleasant sensation. While the exact cause of RLS is still unknown, the syndrome is typically treated with dopaminergic drugs — medications that replace or prevent the loss of dopamine — that have a high initial effect but over time lose their effectiveness.

“The problem is that patients on these dopaminergics eventually develop a side effect called augmentation,” Clemens said. “Their symptoms get worse while taking the current medication used for treatment.”

Classic RLS treatments act on a dopamine receptor known as D3 that has a suppressive effect in the nervous system. However, Clemens’ lab has shown in animal models that over time this medication leads to an increase of a different, excitatory receptor subtype, D1. This increase of the D1 receptor might be the cause of augmentation.

Clemens’ patent proposes a new treatment method that targets the increased D1 receptor levels in RLS patients suffering from augmentation, leading to reduced activation of D1 receptors while providing traditional therapy relief from RLS.

“Our lab postulates that this new compound will maintain long-term efficacy for RLS,” Clemens said. “If augmentation begins, we predict that we can reduce D1 receptor activation in patients and balance things back out, keeping the treatment effective.”

Clemens was awarded a grant from the North Carolina Biotechnology Center to run a small pilot study with a collaborator from the University of Houston using this new treatment method.

This work has gained the attention of a company that has interest in establishing a partnership where ECU’s patent rights may be used in combination with its existing drug formulation to bring relief to RLS patients suffering from augmentation.

Clemens added that the idea to apply for a patent came from ECU’s Office of Licensing and Commercialization.

“They not only brought the idea of patenting our research to my attention, but they also helped me through the process and handled all of the legal and technical aspects of filing a patent,” he said. “The patent would not have been issued without their help. I now know that it can be very beneficial to have experts in other areas come from different angles that make us think of other ways to use our work.”

Marti Van Scott, director of licensing and commercialization, said that finding commercialization opportunities for faculty research is an important bridge that brings science into the communities the university serves.

“It is a pleasure to work alongside our faculty to identify translational research opportunities that have potential to make a meaningful impact,” Van Scott said. “Licensing and commercialization works hard to identify skilled development partners to offer essential guidance for these translational activities. Whether it’s a new therapeutic or medical device, teaching or training method, or research tool, we are available to support the campus research and innovation ecosystem.”

While Clemens’ lab continues to work on its RLS treatment, Clemens said he’s also continuing to work on other medical treatments, including care for opioid pain tolerance.

Breakthrough in treatment of restless legs syndrome

Press release:

New research published in the Journal of Physiology presents a breakthrough in the treatment of Restless Legs Syndrome (RLS).

RLS is a common condition of the nervous system that causes an overwhelming irresistible urge to move the legs. Patients complain of unpleasant symptoms such as tingling, burning and painful cramping sensations in the leg. More than 80% of people with RLS experience their legs jerking or twitching uncontrollably, usually at night.

Until now it was thought that RLS is caused by genetic, metabolic and central nervous system mechanisms. For the first time the researchers show that, in fact, it is not only the central nervous system but also the nerve cells targeting the muscles themselves that are responsible.

This new research indicates that the involuntary leg movements in RLS are caused by increased excitability of the nerve cells that supply the muscles in the leg, which results in an increased number of signals being sent between nerve cells.

Targeting the way messages are sent between nerve cells to reduce the number of messages to normal levels may help prevent the symptoms of RLS occurring. This could be achieved by new drugs that block the ion channels that are essential for the communication between nerve cells.

The research conducted by the University of Gottingen in conjunction with the University of Sydney and Vanderbilt University involved measuring the nerve excitability of motor nerve cells of patients suffering with RLS and healthy subjects.

The next step is to investigate the effect of different medications in patients and the effect on RLS.

Dirk Czesnik, corresponding author of the study, commented on the findings:

‘Patients who suffer from Restless legs syndrome complain of painful symptoms in the legs leading to sleep disturbances. The mechanisms for RLS are still not completely understood. We have shown that also the nerve cells supplying muscles in the leg are responsible and hereby additional drug treatments may be ahead targeting these nerve cells.’

Foot wrap offers alternative to medication for patients with restless legs syndrome

Press release:

Authors from Lake Erie Research Institute in Pennsylvania report an adjustable foot wrap caused to treat restless legs syndrome (RLS) is 1.4 times more effective than the standard pharmaceutical treatment. The pilot study published today in The Journal of the American Osteopathic Association.

The eight-week clinical trial involved 30 otherwise healthy adults with moderate to severe restless leg syndrome. Researchers studied Clinical Global Impression responses as well as the mean change in the International Restless Leg Syndrome Study Group Study Scale (IRLSSGS). A meta-analysis was then used to compare the RLS device with three historic studies of the medication ropinirole and a placebo.

Clinical Global Impression responses indicated significantly greater improvement with the RLS device (90 percent) compared with ropinirole (63 percent), the current standard dopamine therapy for RLS. Additionally, change in IRLSSGS score was significantly greater for the RLS device (17.22) compared to historic reports for ropinirole versus the placebo (12 versus 8.9 respectively). Patients using the RLS device also reported an 82 percent decrease in sleep loss.

The RLS device was designed to put adjustable targeted pressure on two muscles in the foot known to relax symptoms of RLS, the abductor hallucis and the flexor hallucis brevis. Researchers indicate that the pressure produced by the device may also stimulate a dopamine release, similar to massage therapy or acupressure.

“By putting pressure on specific muscles in the feet, we are able to create a response in the brain that relaxes the muscles activated during RLS,” said Phyllis Kuhn, MS, PhD, and the study’s lead researcher. “It’s a near perfect example of the body regulating itself without drugs, many of which have the potential for significant adverse side effects.”

Restless leg syndrome (RLS) is a neurologic disorder causing unpleasant sensations and an urge to move the legs when at rest. The sleep loss associated with RLS can cause extreme fatigue, anxiety and depression. According to the National Institute of Health, RLS may affect as many as 10 percent of the U.S. population, with more than nine million experiencing moderate to severe symptoms.

Until recently, potent drugs including opioids, depressants and dopamine agonists have been used to ease symptoms, but each of these is accompanied by negative side effects such as dizziness, nausea, vomiting and the added risk of addiction.

“Restless legs syndrome really erodes quality of life because it causes extreme fatigue for many patients. As an osteopathic physician, it’s a challenge to balance the need to restore sleep while preventing additional harm from medication. These results show promise in otherwise healthy individuals for a nonpharmaceutical option that appears to have rather minor, temporary adverse effects for some users,” said Rob Danoff, DO, an osteopathic family physician and program at Aria Health Care in Philadelphia.

Adverse effects were reported by seven patients in the study. The effects included pain (1), pins and needles sensation (2), irritability (3), spasm (1) and warm feet (1).