Restless Legs Syndrome Foundation Blog

May 5, 2021

By Stefan Clemens, PhD, HdR, Chair, Research Committee, RLS Foundation Scientific and Medical Advisory Board

The RLS Foundation’s Research Grant Program is a return-on-investment initiative; member contributions lead to advances in the understanding of RLS and to potential improvements in treatment options. The RLS Foundation established the Research Grant Program in 1997 under the leadership of Bob Waterman (Board of Directors member with two terms as Board Chair, 1995–2005 and 2011–2019). The idea was to award small research grants seed funding to provide the critical data necessary to secure additional research grants from national and international agencies.

The first research grant was awarded in 1999. Since then, an average of about two projects per year have been funded. To date, 48 grants have been supported by the RLS Foundation, totaling nearly $2 million in research funding. These 48 projects were carried out by 41 clinicians and researchers. Their findings have led to over 25 publications in a wide range of neurological and neurobiological journals and books. More importantly, the seed-funding grants provided by the RLS Foundation have led to over $10 million in additional grant support from other sources, thereby further strengthening research in the field of RLS.

Research grant applications are first reviewed by the RLS Foundation’s Scientific and Medical Advisory Board (SMAB); details about its members can be found at www.rls.org/SMAB. The SMAB consists of both clinicians and basic science researchers who are responsible for monitoring RLS medical and scientific research issues and bringing their respective expertise to the grant review sessions. In addition to reviewing research grant applications, the SMAB reviews all Foundation publications and advises the RLS Foundation’s Board of Directors on issues of medical or scientific interest and importance. A group of external specialists approved by the SMAB has agreed to serve as grant reviewers to strengthen the rigor of the research supported by the RLS Foundation and to provide additional guidance. Research grant proposals that receive a favorable decision by the SMAB are then presented to the RLS Foundation’s Board of Directors for funding consideration.

Since its inception, the grant program has focused on specific areas of study: genetics, epidemiology, iron regulation, neurophysiology, the development of novel treatment options and RLS animal models. Based on the findings of research in these areas, the SMAB recently developed new guidelines and funding priorities for future grant proposals that are summarized here:

Brain Iron Homeostasis: RLS is regularly associated with changes in brain iron function.

• Research Target: Elucidate the biological factors that contribute to RLS-relevant alterations in iron homeostasis in the nervous system.

Genetic/Epigenetic Factors: Multiple studies have underscored the role of specific genetic and epigenetic factors in the development of RLS. Genetic factors refer to factors that stem from familial heredity or gene mutations; epigenetic factors refer to changes in a person’s genome as a function of, for example, exposure to environmental factors.

• Research Target: Identify genetic and epigenetic factors and their interactions in RLS patients and develop animal models in which these interactions can be better explored in mechanistic detail.

Comorbidities: RLS is often associated with a wide range of other neurological and non-neurological diseases. What is the impact of RLS on other ailments such as cardiovascular disease, sleep apnea or Parkinson’s disease?

• Research Target: Identify any possible causal links between RLS and these other diseases.

Neurobiological Interactions: A variety of signaling molecules have been identified in the nervous system that are changed with RLS. It is often unclear, however, if the changes in these signaling molecules are themselves causing RLS symptoms or if they are a result of other changes.

• Research Target: Identify RLS-relevant neurotransmitters and neural pathways that may be implicated in RLS.

Therapeutics, Pharmacological Treatments and Therapeutic Responsiveness: A wide range of medications is used to treat RLS, and many of these compounds can lead to unwanted side effects, such as tolerance or augmentation.

• Research Target: Explain the pharmacology of existing RLS medications, develop novel approaches that show better efficacy or fewer side effects, and generally advance knowledge toward development of better treatments of RLS.

Nonpharmacological Treatments: In addition to current pharmacological treatment options, RLS patients may find benefit from nonpharmacological approaches. These include, but are not limited to: transcranial or spinal magnetic or electric stimulation; transcranial direct current stimulation; cognitive behavioral therapy; and intermittent compression of the lower limbs.

• Research Target: Describe the mechanisms in nonpharmacological treatments that lead to the improvement of RLS symptoms.

Novel Diagnostic Markers: Identifying RLS relies on the subjective feedback of a patient to their clinician.

• Research Target: Develop better assessment techniques or devices that will provide improved outcome measures for clinical research.

The RLS Foundation plans to open a new series of biannual calls for submissions of research grant applications with rotating main themes, in which submissions will be prioritized around the above-listed research areas. The RLS Foundation will also be seeking grant submissions from specialists in these respective areas, to increase the scientific depth and widen the breadth in RLS-related research. Additionally, the RLS Foundation has set aside funds for one predoctoral or postdoctoral fellowship grant per year to attract promising young investigators to the field. To contribute directly to that fund, go to www.rls.org/AllenFund.

These changes to the RLS Foundation’s Research Grant Program will improve our understanding of RLS in the clinic, spearhead new approaches and treatments in the lab, identify new and emerging drugs and technologies, and improve patient outcomes by engaging an increasing number of clinicians and researchers dedicated to finding a cure for RLS.

December 10, 2020

The RLS community has lost a giant in the field of Sleep Medicine and RLS research, Dr. Richard P. Allen.

Richard P. Allen, PhD, was a professor of neurology at Johns Hopkins University in Baltimore. He founded and served as the co-director of the Johns Hopkins Center for Restless Legs Syndrome, one of the Foundation’s certified RLS Quality Care Centers. Dr. Allen was a diplomate of the American Board of Sleep Medicine and founder of the International Restless Legs Study Group (IRLSSG).

In his dual roles as a clinician and researcher, he dedicated his life's work to RLS education, management, and treatment. He was instrumental in creating the RLS diagnostic criteria and rating scales for use in clinical and research settings, using consensus guidelines to provide state of the art care to RLS patients.

Research is an active part of the sleep medicine program at Johns Hopkins. Dr. Allen authored or co-authored 661 peer-reviewed RLS journal articles that include the consensus guidelines for the iron treatment of RLS, prevention and treatment of dopaminergic augmentation, genetics, and the RLS glutamate relationship. He authored book chapters, and editorials, as well as chairing NIH sections and symposiums on RLS.

RLS Foundation Executive Director, Karla Dzienkowski spoke of his importance to the field. "Dr. Allen was the leading expert in the field of RLS. He was respected and admired by his peers, who relied on his insight as a researcher and clinician. We will all miss him, especially the patients who were the recipients of his outstanding care."

Dr. Allen served as Chair of the Foundation's Medical Advisory Board during 1998 to 2000, served on that Board through 2008, and made significant contributions to the RLS Foundation. In 2000, he received the Foundation’s Ekbom Award, the highest award given to an individual who has enhanced the lives of those living with the disease.

The RLS Foundation has set up the Richard Allen Memorial Fund to be used to further RLS research. To contribute and honor Dr. Allen’s memory go to www.rls.org/AllenFund.

October 1, 2020

East Carolina University associate professor receives patent for treating Restless Legs Syndrome

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.

Stefan Clemens, PhD, HdR, focuses his research on investigating the neural networks in the spinal cord, especially their role in neurological disorders, like RLS. He studies the role of dopamine in the spinal cord, and how the interactions between its different receptor subtypes may play a role in augmentation. At the RLS Foundation, Dr. Clemens serves on the Scientific and Medical Advisory Board where he chairs both the Brain Bank Committee and the Research Grant Committee.

August 28, 2020

Take the RLS Patient Odyssey Survey to help advance RLS research, treatments and awareness!

On Sept. 23, RLS Awareness Day, the RLS Foundation will launch a new research study on the challenges of living with RLS. The RLS Patient Odyssey Survey II will evaluate RLS treatment strategies, emotional well-being, relationships and lifestyle, adding to the body of knowledge about the burden of disease and identifying focus areas for future education and research.

Specifically, the study aims to:

• Understand the experiences of RLS patients with medical treatment and symptom management
• Provide data to researchers on the long-term burden of disease, including impact on spouses and partners
• Promote awareness that RLS is a serious neurological disorder
• Provide resources for RLS patients to help facilitate decision-making with their healthcare providers on medical treatments to manage their disease

RLS Patient Odyssey Survey II is the second survey developed by the RLS Foundation. Findings in the 2013 first survey were published in the the Journal of Sleep Medicine and disseminated broadly. RLS Patient Odyssey Survey II will gather updated and expanded data in areas such as symptom management, experience with healthcare providers, and ways in which the disease affects daily life and emotional well-being.

The current survey is particularly focused on the RLS patient experience, especially with regard to treatments and medical care. The survey was designed by a work group comprised of RLS Foundation Scientific and Medical Advisory Board members Brian Koo, MD, William Ondo, MD and John Winkelman, MD; Board of Directors member Jeffrey Durmer, MD, PhD; and staff members Karla Dzienkowski, Maddie Lionberger and Zibby Crawford. The survey is made possible thanks to an educational grant from Arbor Pharmaceuticals.

RLS Foundation members and nonmembers alike are encouraged to participate in the study, which will consist of two online surveys: one for RLS patients, and one for partners. To participate, visit www.rls.org/odyssey from Sept. 23 to Oct. 23. See below for details. Survey results will be shared with the RLS community and the public in 2021, prepared for publication in the medical literature, and presented in scientific meetings. Findings will also be shared with health policymakers in Washington, DC in the RLS Foundation legislative agenda and advocacy materials.

“RLS is a serious disease that can have a devastating impact on quality of life,” says Karla Dzienkowski, executive director of the RLS Foundation. “We have come a long way to advance treatments and research, but today's treatments are limited, and there is no cure. RLS patients still face significant, daily challenges in managing the disease. This study will provide data to accelerate and focus our efforts to address these challenges and improve quality of life for RLS patients and future generations of their families.”

We need you to help advance RLS research, treatment and awareness by taking the Patient Odyssey Survey!

Your voice matters! You live with RLS every day, and your input is critical to helping researchers, healthcare providers and policymakers understand the impact of RLS on daily life and where to focus their efforts.

Here’s what you need to know:

• Access the survey starting on RLS Awareness Day: Wednesday, Sept. 23, at www.rls.org/odyssey.
• There are separate surveys for RLS patients and their spouses/partners (living in the same household).
• The patient and partner surveys take about 45 and 20 minutes to complete, respectively. You do not have to complete the survey in one sitting.
• You do not need to be a member of the RLS Foundation to participate.
• The surveys are anonymous; no individual identifying information is requested.
• We strongly encourage everyone to take the online survey, if possible. However, those without internet access or in need of accommodations can request a mail-in survey. Contact the RLS Foundation at info@rls.org or 512-366-9109.
• The last day to participate is Friday, Oct. 23.

Mark your calendar for Sept. 23 to take the survey, and please share the link with others. You can also visit www.rls.org/odyssey to download a one-page flyer to hand out or post on bulletin boards in your community. Thank you!

Questions? Contact Maddie Lionberger, Research Coordinator, at maddie@rls.org or at 512-366-9109.

July 30, 2020

Why Your Voice Matters

By Kris Schanilec

Your advocacy efforts have been paying off! In October 2017, the RLS Foundation launched an advocacy initiative to inform federal policy makers about restless legs syndrome (RLS) with three main goals in mind: increasing funding for research, protecting appropriate access to opioid therapy, and expanding physician education and public awareness.

Many members of the RLS community have done their part in pursuing these goals by reaching out to their federal and local representatives via email, letter or phone – as well as joining the Foundation in Washington, DC, last May for RLS Advocacy Day on Capitol Hill. As a result, Congress continues to highlight RLS medical research at the National Institutes of Health (NIH) through report language in annual appropriations bills; and the Department of Defense continues to pursue important research on sleep disorders.

You may be wondering, “How does this affect me?” Educating legislators about the concerns of RLS patients puts necessary pressure on Congress to continue funding major research institutions, which in turn allocate resources to further research on RLS and sleep disorders in general – bringing scientists closer to finding better treatments and ultimately, a cure.

The proof is in the grant allocations that have been awarded to key researchers in the field, including members of the Foundation’s very own Scientific and Medical Advisory Board. Brian B. Koo, MD, who is the director of the Yale Center for Restless Legs Syndrome (an RLS Quality Care Center), recently received a grant from the Department of Defense for his work on RLS and hormones. Dr. Koo and his team at Yale University are investigating whether the levels of melanocortin hormones are increased in the blood and cerebral spinal fluid of people with RLS. If you are interested in participating, see details on www.rls.org.

Likewise, RLS Foundation advisory board member James Connor, PhD, at Penn State University received a grant from the National Institute of Neurological Disorders and Stroke to investigate iron deficiency and the RLS brain, in collaboration with David Rye, MD, PhD, and Lynn Marie Trotti, MD, MSc, both of Emory University. Dr. Trotti is the director of the Emory Sleep Center – an RLS Quality Care Center. Together, these researchers have developed models that will help to determine how cerebral spinal fluid from RLS patients affects the iron transport at the blood brain barrier.

Also funded by the NIH are RLS Foundation advisory board member Kathy Richards, PhD, RN, FAAN, of the University of Texas; and Christine Kovach, PhD, RN, FAAN, of the University of Wisconsin. They received a large grant from the National Institute on Aging to improve the treatment of nighttime agitation in people with Alzheimer’s disease. The researchers hypothesize that RLS may be a cause for nighttime agitation and sleep disturbance in these individuals.

These experts have made significant advances in the field of RLS research. Dr. Koo is one of the world’s foremost experts on the epidemiologic research that links periodic limb movements during sleep and cardiovascular disease. Dr. Connor is a leader in understanding the cellular and molecular mechanisms by which cells regulate iron. Dr. Rye was part of an international team that identified the first gene variant associated with RLS. And, Dr. Trotti is a two-time recipient of the American Academy of Sleep Medicine Foundation Strategic Research Award for her work on central disorders of hypersomnolence, RLS and sleep in neurodegenerative disease.

In addition to their work in research, these experts also work directly with the RLS Foundation to increase their impact on the RLS community. Drs. Connor, Koo and Trotti are all members of the RLSF Scientific and Medical Advisory Board. Dr. Koo and Dr. Trotti serve as the directors of the Yale Center for Restless Legs Syndrome and the Emory Sleep Center, respectively. Dr. Rye is a certified RLS provider at the Emory Sleep Center. Finally, Dr. Koo and Dr. Trotti play a significant role in educating the public, as the medical editor of NightWalkers and the author of the “In the News” column, respectively.

RLS Foundation Scientific and Medical Advisory Board member John W. Winkelman, MD, PhD, of Harvard University; and board member Jeffrey Durmer, MD, PhD, of Fusion Health; have attended numerous meetings with policy makers to advocate the needs of RLS patients.

Christopher Earley, MB, BCh, PhD, FRCPI, also adds a powerful voice to RLS advocacy in Washington. Dr. Earley is not only the chair of the RLS Foundation’s Scientific and Medical Advisory Board, but also the director of the John’s Hopkins Center for Restless Legs Syndrome, an RLS Quality Care Center. He has joined the RLS Foundation in Washington on multiple occasions to advocate for the needs of RLS patients, healthcare providers, and researchers. Dr. Earley is conducting an NIH-funded study to evaluate epigenetic changes in DNA from blood (lymphocytes) and from brain autopsy in individuals with and without RLS.

Here is Dr. Earley’s take on the recently funded research projects: “The truth is, restless legs syndrome is something that most people don’t know about, and definitely very few people understand. When it comes to competing for grant-based money whether through the National Institutes of Health, National Science Foundation, or Department of Defense, name recognition is important. The RLS Foundation’s presence in Washington, DC, has been very important in enhancing visibility of the name and the disease. This gives us a fighting chance for competitive grant money when measured up against heart disease, cancer, and neurological conditions like Alzheimer’s disease. Further work is needed. Each visit to Washington increases the possibility of giving RLS higher visibility on grant-supported initiatives.”

January 25, 2019

Study Funded by RLS Foundation Reveals Results

By Kris Schanilec

Scientists are one step closer to developing a working animal model of RLS. In a study funded by the RLS Foundation, Yuan-Yang Lai, PhD, and her team at the University of California – Los Angeles (UCLA), researchers manipulated the diet of rats to make them iron deficient, and the animals demonstrated symptoms of RLS. These symptoms improved when the rats were given the drug pramipexole, and when they received more iron in their diets – two therapies known to improve RLS in humans.

“Dopamine drugs are one of two first-line treatments for RLS; however, they can lead to adverse effects, such as augmentation, after use,” says Dr. Lai. “Using our animal model, we should be able to test alternative drugs that are developed for the potential treatment of RLS that is caused by iron-deficiency anemia.”

The model may also enable researchers to identify the specific brain regions, circuits and chemicals involved in RLS and periodic limb movements disorder (PLMD). The study, “Motor Hyperactivity of the Iron-Deficient Rat – An Animal Model of Restless Legs Syndrome,” was published August 2017 in the journal Movement Disorders.

Studies have shown that RLS is common in people with iron-deficiency anemia, affecting up to 32 percent of people with this condition. The researchers fed rats an iron deficient diet to create anemia, then recorded their motor activity, or movement, through implanted electrodes – before and after treatment with pramipexole. They also monitored the animals after feeding them a normal diet to restore their iron stores, representing the process of iron therapy in humans.

The researchers found that the iron-deficient animals had symptoms similar to those seen in RLS patients, including motor hyperactivity in quiet wake and in sleep, frequent awakening from sleep, and daytime sleepiness. These symptoms were relieved when the rats received pramipexole, as well as when they received a normal diet containing iron.

These findings build on those of a previous RLS Foundation-funded study in which Dr. Lai found that iron-deficient rats given thioperamide, an H3 receptor antagonist, showed reduced period limb movements (PLMs). As a next step, Dr. Lai’s team is currently using the animal model to study why pramipexole treatment causes augmentation, and which areas and chemicals of the brain are involved in RLS.

December 14, 2018

By Kris Schanilec

New research has found that nerve activity outside the central nervous system may play a role in restless legs syndrome (RLS) symptoms.

In a study published in the Journal of Physiology, scientists report that nerve cells supplying muscles in the legs behave differently in people who have RLS.

Until now, RLS research and treatment has focused largely on processes deep within the brain. First-line RLS treatments target the brain's dopamine and glutamate systems, and brain iron deficiency is also known to be a factor in RLS.

In the new study, the researchers applied electrical stimulus to motor and sensory axons (or nerve fibers) of the median nerve, which is one of the major nerves along the arm. Study participants who had RLS showed higher activity in the motor axons but not the sensory axons, compared to participants who did not have RLS. In their paper, the researchers stated, “Taken together, our results suggest an increase in the excitability of motor units in RLS that could enhance the likelihood of leg movements.”

While the study was small, involving 33 RLS patients and 38 healthy controls, its findings open new avenues for exploration – including medications that could be developed to potentially treat RLS by targeting the nervous system outside the brain and spinal cord.

The research was conducted by the University of Gottingen in German, in collaboration with the University of Sydney in Australia, and Vanderbilt University in the US. RLS Foundation Scientific and Medical Advisory Board member Art Walters is a co-author of the study.

AUGUST 16, 2018

What You Should Know about Iron and RLS

Iron deficiency is a known contributing factor to RLS, and many find some symptom relief from supplemental iron in pill form or by intravenous (IV) infusions.

Healthcare providers have new guidance for treating RLS patients whose iron stores are low. A paper published in the January 2018 issue of Sleep Medicine provides information on how to evaluate RLS patients for low iron, when to offer iron therapy as a treatment, and which type of treatment is most likely to be helpful for individual patients, including children.

“Iron treatment, despite its importance, is not well understood,” says co-author Richard P. Allen, PhD, a researcher at the Johns Hopkins Center for Restless Legs Syndrome. “Iron treatment is complicated by current iron status, and the various oral and IV iron treatments available. Understanding the benefits of IV iron in particular for some patients is relatively new, and this paper provides reasonable guidance for its use that is not available elsewhere.”

Past research has shown that iron deficiency in the brain is an underlying abnormality of RLS. “RLS treatments are basically palliative – they reduce symptoms but do not reduce any basic biological abnormality,” Allen says. “Iron treatment differs. It serves to reduce, for some, a biological abnormality in RLS of reduced brain iron.”

The new report was developed on behalf of the International Restless Legs Syndrome Study Group (IRLSSG). In recent years, a number of research studies on iron for RLS and periodic limb movement disorder (PLMD) have been published. To evaluate these findings, the IRLSSG formed a task force of 12 medical experts in RLS, sleep medicine, neuroscience and other fields, to evaluate published research on the topic and develop a set of recommendations for clinical practice.

This group searched the medical literature and examined 299 related articles. The group’s analysis also included clinical recommendations based on expert clinical opinion. The resulting report includes evidence- and consensus-based guidelines that confirm iron should be a first-line treatment option for RLS. The report also recommends treating people with RLS and iron deficiency with oral iron first, unless there is a medical reason why oral iron cannot be used. The article presents updated treatment algorithms for iron use to treat RLS in adults, and both RLS and PLMD in children.

Importantly, the article delves into the differences among five different IV iron formulations available. “Not all IV iron formulations are alike, and some appear to work better than others,” says Dr. Allen. In addition, specific guidance about when and how to use oral iron is presented, including the recommendation that taking oral supplements once a day is preferable to taking them twice a day.

The article, “Evidence-based and consensus clinical practice guidelines for the iron treatment of restless legs syndrome/Willis- Ekbom disease in adults and children: an IRLSSG task force report,” is available online at www.sleep-journal.com.

This and other clinical publications are the outcome of dedicated work by members of the RLS medical and scientific community to help healthcare providers worldwide offer the best possible medical treatment to RLS patients.

Iron and RLS: What you need to know

Every individual with RLS should have their blood iron levels (serum ferritin) checked, as keeping ferritin levels mid-range – at 75 micrograms per liter and above – correlates to RLS symptom improvement.

If your iron levels are low, your doctor may recommend ways to replenish your iron stores, including:

• Increased consumption of iron-rich foods, especially meat, fish and liver. Leafy green vegetables also contain iron but may not be broken down adequately by your digestive tract to deliver significant amounts of iron to your body.
• Oral iron supplements. For best iron absorption, iron pills should be taken at night on an empty stomach with vitamin C. They should not be taken with food, milk, antacids, calcium supplements or medications used to treat acid reflux and thyroid.
• IV iron therapy. Your RLS doctor should be aware of the potential for IV iron treatment, and if you are an appropriate candidate, can refer you to a hematology center or RLS program that provides iron treatments for RLS.

Iron supplements should only be taken under the supervision and care of a physician to ensure proper monitoring and help prevent iron overload.

Learn more

To learn more about iron and RLS, please view the webcast “Iron and RLS” or see the handout Understanding Iron and Restless Legs Syndrome, available in the Member Portal at www.rls.org.

JULY 21, 2018

By Kris Schanilec

If you have RLS, you know the relentless leg discomfort that can drive you out of bed at night.

Chances are, you also have two other symptoms: periodic limb movements in sleep (PLMS) – 80 percent of those suffering from RLS display this symptom; and constant wakefulness or “hyperarousal” – people with RLS typically are not sleepy during the day, even if they don’t sleep well at night.

Now, scientists have gained new insight into what causes these symptoms – and new avenues to investigate for treatment.
In 2014 and 2015, Sergi Ferré, MD, PhD, of the National Institute on Drug Abuse (Intramural Research Program) received grants from the RLS Foundation to more closely examine how dopamine and glutamate work in the brain.

Dr. Ferré has found that low levels of receptors of adenosine, a chemical in the brain that regulates neurochemicals, lead to abnormally high levels of glutamate and dopamine. This may be the underlying cause of both PLMS and hyperarousal in RLS. The researchers have also pinpointed a subtype of receptor in the brain – the dopamine D4 receptor – as a new and better target for dopamine drug development.

These findings are the culmination of a four-year study funded by the RLS Foundation, and were recently published in Annals of Neurology¹ and Frontiers in Neuroscience.²

Building on decades of RLS research

Dr. Ferré’s research into RLS builds on decades of science by others on the roles of dopamine and glutamate in the brain for those who suffer from RLS.

It has long been believed that RLS is related to a malfunction in the way the brain uses dopamine. Dopamine is a neurotransmitter (a brain chemical that sends messages) associated with muscle activity and movement. Dopamine medications for RLS act by decreasing the amount of dopamine produced by neurons (brain cells). This has the effect of reducing PLMS. However, use of dopamine medications is limited by the serious side effect of augmentation.

In 2013, scientists at Johns Hopkins identified the involvement of another neurotransmitter – glutamate, which is associated with arousal (wakefulness). Researchers found elevated levels of glutamate in the brains of people who had RLS. The extra glutamate is thought to contribute to PLMS – and to hyperarousal. Many RLS patients take alpha-2-delta medications to control their symptoms by reducing glutamate levels.

In the current study, Dr. Ferré’s laboratory used its first RLS Foundation grant to create an animal model that will help develop and test new RLS treatments. A rodent was fed an iron-deficient diet to mirror the brain iron deficiency found in people with RLS. The researchers invented a method that combines optogenetics and microdialysis. They attached a light-activated protein to specific neurons between the cortex and striatum in the brain of the rodent. When they shone a light on the neurons, this triggered the release of glutamate – which was greater in the animals with iron-deficiency than in animals fed a regular diet.

“The first finding was to show that in the rodent with brain iron deficiency, a well-accepted pathogenetic model of RLS, we were able to show that brain iron deficiency produces increased sensitivity of the cortico-striatal terminals to release glutamate,” says Dr. Ferré. Recently, Dr. Ferré’s team tested this animal model with several RLS drugs: the dopamine agonists pramipexole and ropinirole, and the alpha-2-delta drug gabapentin. The researchers validated that these medications work by counteracting the release of glutamate.

In the process, the team also pinpointed a specific type of protein, called the dopamine D4 receptor, that controls the transmission of glutamate in these cells. This protein may be an effective target for future dopamine medications. “Thanks to this mechanism, we were able to find which subtype of dopamine receptor needs to be targeted,” says Dr. Ferré. “I believe that augmentation is acting on other subtypes. That opens up new hope for therapeutic approaches that probably will have less secondary problems like augmentation and will be more successful.”

Uncovering a new player: Adenosine

If RLS medications work by reversing unusually high dopamine and glutamate levels, how could these high levels be prevented in the first place?

That is the scientific question – and Dr. Ferré feels he may have found an answer in adenosine. Adenosine is a neurotransmitter that regulates the levels of other chemicals; it acts as a brake for the dopamine and glutamate systems in the brain.

Using the animal model, Dr. Ferré’s team found that when there are fewer adenosine receptors (specifically of the A1 subtype), there is increased dopamine and glutamate. This links adenosine to PLMS symptoms.

But there’s more. “Adenosine by the way, regulates the sleepiness associated with prolonged wakefulness,” explains Dr. Ferré. In the cortex, thalamus and other areas of the brain, adenosine modulates homeostatic sleep. Low levels of adenosine receptors could explain the hyperarousal of RLS. “The beauty of the adenosine story is that it connects the hyperarousal symptoms with movement [PLMS],” he says.

“What is really important about our story is that maybe we have found a mechanism – the adenosine system – that links brain iron deficiency to hyperglutamatergic and hyperdopaminergic states.”

This insight can be used to potentially develop RLS treatments that increase the concentration of adenosine to prevent both PLMS and hyperarousal. One such drug is already available clinically: dipyridamole, an antiplatelet drug that protects against stroke and heart attack.

Dr. Ferré’s team validated dipyridamole using the animal model. He also collaborated with Diego García-Borreguero, MD, PhD, director of the Sleep Research Institute in Madrid, to trial the drug in a small group of RLS patients – with promising results. As a next step, Dr. García- Borreguero will coordinate a larger clinical trial in Europe.

Dr. Ferré is also working with several research laboratories to pursue drugs similar to dipyridamole that are more potent and can more easily cross the blood-brain barrier.

“The story now reaches the clinical level,” says Dr. Ferré. “Anything else that could modify the release of glutamate by those terminals could theoretically be good therapeutically for RLS. That’s the case with dipyridamole. We just got results that validate once more our animal model and, in fact, dipyridamole decreases glutamate release by cortico- striatal neuronal terminals.”

Study Results At a Glance

• Using a rodent model of RLS, the researchers showed that people with RLS may have an increased sensitivity in specific brain cells to release dopamine and glutamate.
• They also found that a decrease in the concentration of receptors for adenosine in the brain may cause higher levels of dopamine and glutamate, explaining movement-related RLS symptoms – namely, PLMS.
• Since adenosine also regulates sleep, the low concentration of adenosine may also explain the hyperarousal symptom in RLS.
• Therapies that increase adenosine may help with RLS. Dipyridamole may be one, and others can be developed.
• The researchers also pinpointed a subtype of protein in the brain that can be targeted by dopamine medications, potentially without augmentation as a side effect.

Thanks to the RLS Foundation

Dr. Ferré credits the RLS Foundation with making the last four years of progress in his laboratory possible. “The RLS Foundation research grant has made what we’ve done so far possible. Above all, it has made it possible for a scientist on our team, Gabriel Yepes, to devote his time entirely to this project. And it has been a complete success.”

He also points to the Foundation’s role in cultivating a community of scientists dedicated to solving the mysteries of RLS who support each other’s work. Forty-four researchers have received grants from the RLS Foundation since 1997, and nine have served on the Foundation’s advisory board. Their work spans several continents and many disciplines. “Thanks to the RLS Foundation, I can connect to different specialties quickly and get their input right away,” says Dr. Ferré.

“We are much closer to understanding the mechanisms of RLS. If you understand the mechanisms, that directs your research,” he adds. “We are very close to getting new approaches – not just new molecules that are acting the same way. We are discovering new mechanisms, and that should open a line to new approaches. To hope.”

¹Yepes G, Guitart X, Rea W, Newman AH, Allen RP, Earley CJ, Quiroz C, Ferré S. Dec 2017. “Targeting hypersensitive corticostriatal terminals in restless legs syndrome.” Ann Neurol 82(6): 951–60. doi:10.1002/ana.25104.
²Ferré S, Quiroz C, Guitart X, Rea W, Seyedian A, Moreno E, Casadó-Anguera V, Díaz-Ríos M, Casadó V, Clemens S, Allen RP, Earley CJ, García-Borreguero D. 2018. “Pivotal Role of Adenosine Neurotransmission in Restless Legs Syndrome.” Front Neurosci 11: 722. doi:10.3389/fnins.2017.00722.

JULY 15, 2018

In June, the RLS Foundation visited Washington for a second round of meetings to advocate for research funding and for continued patient access to opioid medications to treat severe RLS.

Led by Executive Director Karla Dzienkowski, the Foundation team met with members of Congress who are on key legislative committees that have jurisdiction over health policy, and with two groups at the National Institutes of Health (NIH).

“Our meetings at Congress and the NIH were very important to moving our advocacy program forward,” Dzienkowski says. “We had the opportunity to meet with Congressional staff who are directly involved in opioid-related legislation. We are also excited to be deepening our relationships at the NIH and taking meaningful steps to advance RLS research.”

The Foundation team met with staff in the offices of Sen. Sheldon Whitehouse, D (RI); Sen. Bob Casey, D (PA); Sen. Elizabeth Warren, D (MA); Rep. Markwayne Mullin, R (OK); Rep. Conor Lamb, D (PA); Rep. Katherine Clark, D (MA); and Rep. Michael Burgess, R (TX).

The discussions centered on the need for a safe harbor for RLS in any upcoming legislation or policy that might restrict access to opioid medications. “Staffers shared that over 50 opioid bills are under consideration,” says Dzienkowski. For the millions of Americans who have chronic, unrelenting RLS, opioid medications taken in low total daily doses can be very effective for controlling symptoms.

The Foundation team also asked legislators to support two research priorities: $2 billion in increased funding for the NIH in fiscal year 2019; and continued inclusion of “sleep disorders” as a category eligible for grants by the Department of Defense.

At the NIH, John Winkelman, MD, PhD, gave a presentation on behalf of the Foundation to the Sleep Disorders Research Advisory Board (SDRAB) of the National Heart, Lung, and Blood Institute. Dr. Winkelman is director of the RLS Quality Care Center at Massachusetts General Hospital and a member of the Foundation’s Scientific and Medical Advisory Board.

The SDRAB is a federal advisory committee that sets the strategy for sleep disorders research at the NIH, and the meeting was an opportunity to highlight the unmet needs of RLS patients. RLS Foundation Board member Linda Secretan is one of two patient advocates on the SDRAB.

In his presentation, Dr. Winkelman discussed limitations of RLS treatments and the importance of research, including his current study to evaluate the long-term use of opioids to treat RLS.

“We had a very positive discussion,” Dr. Winkelman says. “It was important to describe the existing landscape of RLS treatment options, particularly as not everyone at the table was fully aware that many people with RLS continue to suffer for a variety of reasons, such as augmentation. It was equally important to raise awareness about the effectiveness of low total daily doses of opioid medications as a therapy for severe RLS.”

The Foundation also visited the National Institute on Drug Abuse and met with members of the Division of Neuroscience and Behavior, which supports research on drug use and addiction. Dr. Winkelman led a lively discussion on the neuroscience of RLS and how new drug therapies might be developed to treat the disease.

“We’re always looking for new ways to intervene to prevent or treat RLS,” Dr. Winkelman says. “We discussed what we already know about what causes RLS in the brain, and the various ways we might learn more about the neurological pathways involved. We came away with new ideas to explore for research.”

The meetings were coordinated by the Health and Medicine Counsel of Washington (HMCW), a government relations organization with nonprofit and healthcare industry expertise that is partnering with the RLS Foundation to guide its advocacy efforts. In addition to Dzienkowski and Dr. Winkelman, the delegation included Kris Schanilec, RLS Foundation communications; and Dane Christiansen, Dale Dirks and Peter Herzog of HMCW.

How You Can Take Action

The RLS Foundation is working hard to advocate on behalf of the RLS community. The Foundation needs you, an RLS patient or family member, to amplify these efforts by meeting with your legislators. You can meet with your members of Congress at offices in your home state or in Washington. Elected officials want to hear directly from their constituents, and sharing your personal experiences is the best way to educate them about the needs of RLS patients.

The Foundation has resources to help you get started. Contact Peter Herzog at herzog@hmcw.org or visit www.rls.org to learn more.

RLS Advocacy: Our Progress

Since October 2017, the RLS Foundation and its partners at HMCW have:

• Delivered letters to members of Congress from 200+ individuals who responded to a request for personal stories about opioid medications and RLS. 
• Attended Congressional meetings and hand-delivered position letters to committees that are crafting legislation related to opioid medications and/or biomedical research funding. These efforts helped support passage of the FY2018 appropriations bill, securing a $3 billion increase in funding to the NIH. 
• Delivered 40 letters to members of the Senate Defense Appropriations Subcommittee from RLS Foundation members who responded to an Action Alert to support inclusion of “sleep disorders” on the Department of Defense Peer Reviewed Medical Research Program in FY2019. 
• Met with 23 Congressional offices, three NIH institutes, the NIH Sleep Disorders Research Advisory Board, and the U.S. Food and Drug Administration (FDA). 
• Coordinated or supported meetings by the RLS Foundation team and Foundation members with US senators and representatives of 13 states.

Why Are Opioids Needed for RLS?

About 1 in 33 Americans – 3 percent of the US population – has RLS that is severe enough to need daily medical treatment. Unfortunately, treatment options are limited, and FDA-approved medications for RLS often have serious, long-term side effects.

When all other options have failed, opioids at low total daily doses are an established, highly effective treatment option for people with RLS. Clinical experience among experts has not shown the degree of drug misuse, dependency or addiction commonly associated with opioid use to treat chronic pain. The RLS Foundation actively conducts educational outreach to help ensure that healthcare providers know how to diagnose and treat RLS, including appropriate use of opioid medications. For more information, visit www.rls.org.

June 21, 2018

By Kris Schanilec

For many people who have Alzheimer’s disease, evenings are difficult. Right around sundown, uneasy feelings and confusion start to flow. The person may become forgetful, agitated – even aggressive, and start pacing or wandering. These symptoms can last through the night and make it tough for anyone in the household to get a good night’s sleep.

Could it be that these behaviors – known as nighttime agitation, or “sundowning” – are caused by RLS? And could treating the RLS lessen the nighttime agitation symptoms?

Researchers led by Kathy Richards, PhD, at the University of Texas at Austin are working to answer these questions. Dr. Richards and co-investigator Christine Kovach, PhD, from the University of Wisconsin-Milwaukee have been awarded a $3.9 million, five-year grant from the National Institute on Aging to evaluate whether there is an association between nighttime agitation and RLS in people who have Alzheimer’s disease.

“Nighttime agitation is the No. 1 reason why people with Alzheimer’s cannot be cared for at home,” says Dr. Richards. “If we can find a better and more precise way to treat nighttime agitation, we can improve the quality of life for many persons who are living with Alzheimer’s disease.”

Nighttime agitation is often treated with powerful antipsychotic drugs, which are only moderately effective and carry with them serious risks, such as falls, stroke and death.

Because nighttime agitation has a strong circadian component and shares symptoms with RLS, Dr. Richards and others have long postulated that for some people, undiagnosed RLS could be the underlying cause. In a previous study led by Dr. Richards, researchers examined symptoms in 59 people who had Alzheimer’s disease and nighttime agitation. They found that 24 percent of participants also had RLS.

In the current research, the team will validate this result in a pilot study – an eight-week, double-blind, randomized controlled trial with 136 long-term care residents who have nighttime agitation and RLS. Participants will receive either gabapentin enacarbil (Horizant, an FDA-approved medication for treating RLS) or a placebo. Data from the study will also help discern the effectiveness, safety and optimal dosage of gabapentin enacarbil for treating nighttime agitation, as well as whether the frequency of RLS symptoms may be linked to nighttime agitation.

The researchers will use a tool newly developed by Dr. Richards called the Behavioral Indicators Test-Restless Legs. This test includes a brief 20-minute observation and simple set of questions for caregivers. Previous studies have shown the tool to be an effective way to diagnose RLS in people who have Alzheimer’s, and one that has potential for future use with children and others who don’t have the ability to report their symptoms.

RLS Foundation Executive Director Karla Dzienkowski visited the University of Texas in May, where she gave a presentation about RLS and met with Dr. Richards’ team to extend the RLS Foundation’s support for the research endeavor. “Cognitively impaired seniors with RLS may have difficulty expressing RLS symptoms causing an inability to sit or lie still during the evening or nighttime hours,” says Dzienkowski. “This study will ensure seniors with cognitive impairments are accurately diagnosed and receive proper treatment to manage their RLS symptoms.”

Dr. Richards emphasizes that while there is no evidence suggesting that RLS causes Alzheimer’s, the study may show that it’s important for caregivers of people with any type of dementia to watch for possible signs of RLS that can then be treated to potentially reduce nighttime agitation.

It all comes down to quality of life for people who have dementia, says Richards. “I hope they will be more comfortable, and that they – and their caregivers – can get a good night’s sleep.”

Kathy Richards, PhD, is a member of the RLS Foundation Scientific and Medical Advisory Board. Read more about her research on the University of Texas at Austin School of Nursing newsletter.

Take Action This Summer!

During the summer, elected officials in Washington break for recess and return to their home states. This is an excellent time to meet with and educate them about RLS, how opioid restrictions are affecting access to necessary treatment, and why more RLS research is needed to find a cure.
The Foundation needs you, a valued and essential member of the RLS community, to join in this important work. Your representatives need to hear your personal story about the struggles of living with RLS. These personal anecdotes put a face to the disease and are crucial to share so that legislators are fully aware of the needs of the RLS community when making legislative decisions.
Not sure where to start? It's easier than you think. The RLS Foundation’s advocacy partners at the Health and Medicine Counsel of Washington (HMCW) are available to assist you in planning and implementing these meetings with your representatives. Contact Peter Herzog at herzog@hmcw.org, or keep reading for information on how to get started.

First Steps

Find out who your representatives are. Each US citizen has three representatives in Congress: Two in the Senate, and one in the House of Representatives. You can find out who they are at www.senate.gov and www.house.gov. Just enter your zip code into the search bar in the top right-hand corner of the page to bring up their names. Many of these officials have offices both in Washington and locally, so select the office closest to you.
Reach out to HMCW. Contact Peter Herzog at herzog@hmcw.org, and he will provide you with talking points, a prep packet and other information to help with the meetings. He may also be able to help schedule meetings.
Make an appointment. Call the office of each representative and request an appointment to discuss issues that you and others with RLS are facing. You will likely be given an appointment with a staff member. Keep in mind that you will be meeting as an individual in the community and not as a representative of the RLS Foundation. If you are a Foundation member, please share this during your meeting.
Strength in numbers. You are not alone! Get a group of friends, family members or other RLS patients to go with you to the meeting. You can also find others who have RLS via the Foundation's Discussion Board, support groups and social media channels.

Resources

While you may have many items that you wish to discuss with your representatives, focusing these particular meetings on issues related to RLS will help make the most impact. The goal is to educate your representatives about RLS, how opioid-related legislation affects you and the RLS community, and why more research funding is needed. The Foundation has a variety of resources to help you accomplish this.
Webinar recordings. The Foundation and HMCW have presented two RLS advocacy webinars, available for free viewing in the "Get Involved" section at www.rls.org. These webinars contain excellent introductory information to RLS advocacy efforts and provide an overview of how you can get involved.
“Statement of Principles.” This document (provided in your prep packet) will be your "North Star" during the meetings and help guide your discussion. While you do not need to memorize all of this information, it will provide the basics about RLS, why more research is needed and why opioid therapies are necessary for patients with severe cases of RLS. Available for free download in the "Get Involved" section at www.rls.org.
HMCW. The Foundation has engaged HMCW staff to guide and focus advocacy efforts on behalf of the RLS community. They are available to help! Email Peter at herzog@hmcw.org with any questions or if you need additional information.

During the Meeting

What to expect. Congressional staff should be friendly and courteous. Remember, they work for you! Their goal is to help you in any way they can, and your “asks” will give them an opportunity to do so. You should arrive 15 minutes early for your meeting and dress in business casual attire. Make sure to print the leave-behind materials beforehand (provided by HMCW or available for download at www.rls.org), as you will be giving them to staff members during your meetings. Keep in mind that you will have 15–20 minutes to make your case, so be ready to start right in with the discussion.
Introductions. Start by thanking the staff member for meeting with you. Introduce yourself and talk about where you are from, then introduce everyone in the group. Be sure to keep the introductions brief so that most of your time is spent educating the representative about the needs of the RLS community. Give the staff member the leave-behind materials to reference during your discussion.
Defining RLS. The person you meet with may not know about restless legs syndrome, so it is important to define what it is. Here is a suggested explanation: “Restless legs syndrome (RLS) is a serious and chronic neurological disease. It causes unpleasant or uncomfortable sensations in the legs, together with an uncontrollable urge to move them. These symptoms can cause severe sleep loss, which can be devastating to a person’s health and well-being, and interfere with work, family and social life. There is no cure for RLS, and treatments are limited.”
Tell your RLS story. How do RLS symptoms impact you day-to-day? What challenges does RLS pose for your work, social life and family relationships? Do you have issues accessing medical care? Everyone's RLS is unique, and it's important to focus on your own experience and how RLS impacts your life.
Introduce the “asks.” Your prep packet provided by HMCW will include a sample meeting outline with specific requests, or “asks,” to make of your legislator. Make sure to review these materials before your meeting. You may want to write down some key points on a note card for reference. In the meeting, state the “asks” clearly and concisely, or read them from the document. Staffers will want to learn how their office can help you, and these “asks” are the best way for them to do so.
Responding to questions. The person you are meeting with may have some questions. If you are asked a complex question that you do not know the answer to, that is okay! Be honest. Let the staff person know that you will find the information and get back to them in a follow-up email.
In the event that you are pressed about RLS patients taking opioids, or you feel that someone is questioning or delegitimizing your struggles with RLS, remain calm and respectful. This will be rare, but it is always good to be prepared. RLS is an underdiagnosed condition, and many people are unaware of its prevalence and severity. Remind the staff person that opioid medications are a last resort for patients suffering from RLS, and that guidelines are available for physicians to prescribe them appropriately. Ask that the staff person review the written materials in the leave-behind packet, which includes the clinical guidelines (“The Appropriate Use of Opioids in the Treatment of Refractory Restless Legs Syndrome”).
Conclusion. Thank the staff member for taking the time to meet with you. The staff member will most likely give you a business card, so be sure to hang onto it for future inquiries. Consider this a relationship-building activity, and plan to follow up with the office a few times a year moving forward. If you brought a camera or phone, ask if you can step outside the office to take a picture together in front of your legislator’s nameplate, to share with the Foundation or on social media. Have fun with it!

After the Meeting

You’ve met with your legislator’s staffer, educated them about RLS, and asked them to support the needs of RLS patients. Give yourself a pat on the back for a job well done!
Make a note in your calendar to follow up by phone or email within two weeks. You can thank the staff person again for meeting with you and provide any follow-up answers to questions. This would also be a great time to plug the Foundation's website at www.rls.org, or share a clip from the Foundation’s YouTube series, My RLS Journey. You can also contact Peter Herzog at herzog@hmcw.org for help with your follow-up messages.


To read more about the Foundation's advocacy efforts, accomplishments, and how you can get involved, visit www.rls.org.

New Connection between Restless Legs Syndrome and Changes in Brain Structure

In a new study published in an online issue of Neurology, researchers at Pennsylvania State University revealed a connection between patients with restless legs syndrome and changes in brain structure, specifically parts of the brain that process sensory information.

"These structural changes make it even more convincing that restless legs syndrome symptoms are stemming from unique changes in the brain, and provide a new area of focus to understand the syndrome and possibly develop new therapies," said study author Byeong-Yeul Lee, PhD, who worked on the research team while at Pennsylvania State University before moving onto The University of Minnesota in Minneapolis. James R. Connor, RLS Foundation Scientific and Medical Advisory Board member, is also an author on this work.

During the study, MRI brain scans were performed on 28 people with severe RLS (who had the disorder for an average of 13 years) and a control group of 51 people without RLS. These scans showed that patients with RLS had an average of 7.5 percent less tissue thickness in the somatosensory cortex, the area of the brain that processes thing like touch, pain, movement, position and temperature.

Interestingly, the RLS patient group also had a decrease in the brain where nerve fibers connect the two hemispheres of the brain. While this study does not prove causation, it does provide a new piece to the puzzle about where to focus RLS research and treatments.

“I think the work is important at two levels,” Dr. Connor said. “The data continue to support that there are differences in the RLS brain --- these types of studies continue to hammer home the idea to the general public and health professional communities and funding agencies that RLS is a biological disorder and not anxiety or something without a biological basis. Additionally, this study is important because it ties imaging to the area of the brain that involves processing sensory information. We don’t know if the RLS symptoms start at this area of the brain or elsewhere in the brain, but for the first time there is a clear change in the brain that interprets sensory input.”

The original Neurology article is available for purchase online.

Opioid Study Still Seeking Participants

Lewis Phelps is current chair of the RLS Foundation Board of Directors. He is a strategic public relations consultant with Sitrick And Company, a Los Angeles-based firm that specializes in handling crisis situations. Previously, Phelps was head of the public relations function for the nation’s second largest electric utility and for two major U.S. rail transportation companies. Early in his career he was a staff reporter for the Wall Street Journal for 10 years.

Phelps has extensive non-profit board experience in addition to a prior six-year term on the RLS Foundation board. He has chaired United Way campaigns in two cities, co-founded an anti-litter organization in Roanoke, Virginia, was on the board and executive committee of the California Science Center for 15 years, and has served as chair of the board of Pasadena Heritage, one of the nation’s leading local historic preservation organizations.

I encourage members of the RLS community to participate in the National RLS Opioid Registry, an important new study that has been funded by the RLS Foundation and is being conducted by John Weyl Winkelman, MD, PhD, and Chief of the Sleep Disorders Clinical Research Program at Massachusetts General Hospital. He is an internationally leading RLS researcher and long-standing member of the Foundation’s Scientific and Medical Advisory Board.

The study seeks to track up to 200 RLS patients who are currently being treated with an opioid medication, and who formerly were treated with a dopamine enhancing drug such as Mirapex or Requip. As of early March 2018, the study is more than halfway toward its enrollment goal.

There’s no monetary payment for participants, but the psychic rewards are large. By joining the study, you can help to significantly increase the body of scientific information that is available on the effectiveness of low dose opioids to treat RLS and the potential side effects. You can also learn how your personal experience with opioids compares with other RLS patients.

While some solid scientific studies address these questions, the Mass General study will expand our knowledge about the efficacy and safety of opioids to treat RLS. Such information will be valuable in coming months and years as the RLS Foundation grapples with the challenges that RLS patients are facing due to growing restrictions on use of opioids.

Addiction is obviously a huge and growing problem in the US. However, available clinical data suggest that using low doses of opioids to treat RLS will not contribute meaningfully to the addiction epidemic.

I can speak from personal experience in saying that participation in the RLS Registry is not difficult, time consuming, or unpleasant; I have become one of the study’s subjects. When you enroll, a researcher will conduct a 45-minute telephone interview with you, at a convenient time. They will ask about your current and former medications used to treat RLS, and your experience with them. The researcher who conducts the interviews is courteous, professional, and pleasant.

Following the initial interview, you will be asked to complete an online survey that takes about 20 minutes, and then you will be asked to complete a similar online survey every six months for up to five years. Your answers to the questions are completely confidential, and all information is kept on a secure hospital database that is only accessible by Dr. Winkelman and his research coordinator.

Each year of the study, you will receive a personal report about the overall results of the study to date, as well as a comparison of your own experience with opioids compared with the study group overall. For example, you will be informed whether your RLS symptoms are controlled better, worse, or about the same as the study group overall.

If you have RLS and are currently being treated with opioids, please do yourself and everyone else who has RLS a favor by joining the study. To do so, simply send an email to rlsregistry@partners.org, in which you identify yourself, provide contact information (email and phone number) and indicate that you wish to volunteer as a study subject.

Thanks,

Lew Phelps, Chair of the RLS Foundation Board of Directors

Help Us Keep Sleep Disorders in Department of Defense Medical Research Program

Action Alert: Residents of Alabama, Alaska, California, Hawaii, Illinois, Kansas, Kentucky, Maine, Mississippi, Missouri, Montana, New Mexico, Rhode Island, South Carolina, Tennessee, Vermont, Washington, and Wisconsin

The Department of Defense (DOD) is finalizing the list of conditions eligible for funding through their Medical Research Program, and we need your help to ensure that sleep disorders like RLS stay on that list! Send us your RLS story about why more research is needed and we will deliver the letter to your legislator.

With your help, we will contact all Senators serving on the Defense Appropriations Subcommittee and ask that they continue to support the inclusion of "sleep disorders" as conditions eligible for study through the Department of Defense Peer-Reviewed Medical Research Program during the Fiscal Year (FY) 2019 appropriations process. 

Background

Each year, the United States Senate crafts an annual DOD appropriations bill, which includes a list of conditions that are deemed “eligible for study” through the Peer-Reviewed Medical Research Program (PRMRP). In order for a condition to be included, Senators need to support the condition and officially ask for its inclusion. Senators have many competing appropriations priorities and in order for them to support a condition-specific request, they need to be educated and asked to do so by their constituents (You).

As a result of grassroots outreach, the Senate has recognized sleep disorders as a condition eligible for study annually for a number of years. This support allows RLS medical researchers to compete for nearly $300 million in federal research funding each year.

Senators are currently working on the FY 2019 DOD appropriations bill and deciding which conditions will be included on the next PRMRP eligible conditions list. Being included on the list one year is no guarantee of being included again in the next year. At this critical juncture, please reach out to the offices of your Senators and ask that they once again support the inclusion of “sleep disorders” in the DOD PRMRP’s eligible conditions list in FY 2019.

Take Action

1. Please consult the list below and see if one of the Senators from your state serves on the Defense Appropriations Subcommittee.

Senate Defense Appropriations Subcommittee Members

Thad Cochran, Mississippi
Dick Durbin, Illinois
Mitch McConnell, Kentucky
Patrick Leahy, Vermont
Richard Shelby, Alabama
Diane Feinstein, California
Lamar Alexander, Tennessee
Patty Murray, Washington
Susan Collins, Maine
Jack Reed, Rhode Island
Lisa Murkowski, Alaska
John Tester, Montana
Lindsay Graham, South Carolina
Tom Udall, New Mexico
Roy Blunt, Missouri
Brian Schatz, Hawaii
Steve Daines, Montana
Tammy Baldwin, Wisconsin
Jerry Moran, Kansas


2. Send us your RLS story via SurveyMonkey!
3. The RLS Foundation will complete the letter template with your story and deliver it to your Senator's office.

Your support is invaluable to the Foundation's advocacy efforts, and we will continue to fight for more funding for research that will help us identify better treatments and a find cure for RLS. You can help make a difference in the lives of thousands living with RLS. Send us your story today!

Don't live in these key states? Your US senators and representatives still want to hear from you – their constituent. It is straightforward and simply a matter of telling your story, sharing your experience and asking them to take your needs into consideration. Want to get involved? Visit the advocacy page of the RLS Foundation website to find out how you can take action now!

March 5, 2018

Giving You A Voice in Washington

By Kris Schanilec

On February 22 and 23, members of the RLS Foundation staff and leadership team traveled to Washington, DC, to advocate on behalf of the RLS community.

The delegation met with staff at the National Institutes of Health (NIH), US Food and Drug Administration (FDA), and Congress. Their goals were two-fold: to educate policy makers about RLS and the need to ensure that RLS patients continue to have access to opioid therapies; and to promote funding for RLS research that will advance better treatments and a cure.

"We are focused on making our collective voice heard in Washington to help ensure continued access to opioids as a treatment for individuals with severe cases of RLS," Executive Director Karla Dzienkowski, RN, BSN, said. "We hope to enhance and expand our advocacy efforts so that no one in our community is denied access to this critical treatment option."

For the millions of people in the US who have chronic, unrelenting, nightly RLS symptoms, opioids may offer the only hope for long-term relief, when all other treatment options have failed. If these patients lose access to opioids, they will lose the ability to manage their symptoms so that they can function in their work and social lives.

During the visit to Washington, the Foundation’s partner, the Health and Medicine Counsel of Washington (HMCW) -- a government relations organization that works with nonprofit organizations and companies in the healthcare industry -- organized opportunities for the RLS Foundation to dialogue with lawmakers, policy makers and others who influence regulations related to opioids and biomedical research.

Day 1: Meetings with NIH and FDA

On February 22, the RLS Foundation hit the ground running. Led by Dzienkowski, the RLS Foundation team included Ronald Barrett, treasurer of the Board of Directors; Dr. Christopher Earley, chair of the Foundation's Scientific and Medical Advisory Board (SMAB); Dr. Michael Silber, SMAB member and head of the Opiate Committee; Kris Schanilec, RLS Foundation communications consultant; Peter Herzog, HMCW legislative associate; and Dale Dirks, HMCW president.

"Our role here is to advocate for an open-minded view on the value of opiates in treating RLS," Dr. Earley said. "It is an important treatment option that needs to be continued and maintained, such that patients with severe RLS, if they need to use these vital medications, are not restricted in any way."

Day one included meetings with leaders of the National Heart, Lung, and Blood Institute (NHLBI), the National Institute of Neurological Disorders and Stroke (NINDS), and the program staff at the FDA.

During meetings with the NHLBI and NINDS (both are institutions within the NIH), the RLSF team discussed ways to increase funding for RLS research and explored possible areas for collaboration. The NIH staff were supportive of the Foundation’s goals and offered many suggestions to explore in follow-up. “The fact that you've taken the time to network with us is a powerful statement," said Dr. Nina Schor, who is deputy director of the NINDS. “RLSF has provided vital input to NINDS in our efforts to support research that will decrease the burden of neurological illness.”

The Foundation shared the challenges of RLS patients who face limited treatment options, and the specific areas where research is needed to discover and test new therapies. The team also stressed the need for both clinical trials of opioid medications and long-term studies on their safety and effectiveness for treating severe RLS.

These meetings were important to building new relationships with individuals at the NIH who can champion the RLS cause and influence decisions about RLS research funding at the NHLBI, NINDS and other institutes within the NIH.

At the FDA, the RLS Foundation met with the office of Public Affairs and Stakeholder Engagement (PASE) at the Center for Drug Evaluation and Research (CDER) to discuss the importance of low total daily dose opioids as an RLS treatment option. The Foundation shared stories of individuals in the RLS patient community who have been taking opioid medications for decades and are encountering barriers to accessing their prescriptions. After highlighting information on new opioid treatment guidelines for patients with RLS, the team stressed the importance of safeguarding access to these medications for RLS patients who genuinely need them.

"The FDA members that we met with recognized the possibility of unintended consequences of heavy-handed restrictions on legitimate opioid use and the potential impact on RLS sufferers,” Barrett said. “Hopefully there will be positive outcomes from our meeting."

Day 2: Championing RLS on the Hill

On February 23, the RLS Foundation team met with Congressional representatives on both sides of the political aisle in 16 Senate and House offices. Meetings included staff members from the offices of Senator Joni Ernst (R-IA), Senator John Cornyn (R-TX), Senator Tina Smith (D-MN), Senator Ted Cruz (R-TX), Representative Rod Blum (R-IA), Representative Tim Walz (D-MN), Representative Roger Williams (R-TX), Representative Mike McCaul (R-TX), Senator Dianne Feinstein (D-CA), Senator Kamala Harris (D-CA), Senator Chris Van Hollen (D-MD), Senator Ben Cardin (D-MD), Representative Judy Chu (D-CA), Representative John Sarbanes (D-MD), and Representative Anna Eshoo (D-CA).

In these meetings, the RLS Foundation delegation explained the specifics of RLS and its devastating effects on the daily lives of millions of Americans. The team delivered nearly 100 letters written by RLS Foundation members, and shared stories that they hear from the RLS community about everyday struggles and increasing issues with access to opioid medications. They stressed the limitations of current treatment options, and that there is no cure for this debilitating disease.

In turn, the RLS Foundation asked that the Congressional representatives support the full $36 billion for NIH funding in fiscal year 2018 so that funds will be available for RLS research and related areas. The Foundation also encouraged the inclusion of “sleep research” as a condition eligible for research grants from the Department of Defense, so that RLS researchers will continue to be eligible for funding through this channel.

Finally, the Foundation pointed to the need for a safe harbor for RLS in any upcoming opioid-related legislation, regulations and policies, so that people with severe RLS who genuinely need opioids to manage their symptoms can continue to access these medications.

These talks were a first step in building relationships with each of the Congressional representatives, and an especially strong connection was sparked with one staffer who has a family member with RLS. The Foundation team will continue to contact these representatives in the coming months to educate them about RLS and the needs of the community.

"It was a very productive visit, and it's just the beginning of our advocacy outreach," Dzienkowski said.

This advocacy trip was an enormous stride for the RLS community and an important milestone in the Foundation’s advocacy initiative. And the fight is far from over. With the help of HMCW, the Foundation will continue to increase awareness among policy makers about the serious nature of RLS, the need for individuals with severe RLS to have access to opioids when they are the best treatment option, and the need for more funding for research that will help identify better treatments and a find cure for RLS.

Your US senators and representatives want to hear from you – their constituent. They are there to represent you. Meeting them is not difficult – it is straightforward and simply a matter of telling your story, sharing your experience and asking them to take your needs into consideration. Want to get involved? Visit the advocacy page of the RLS Foundation website to find out how you can take action now!