Restless Legs Syndrome Foundation Blog

May 28, 2021

In-Person and Virtual Meetings

By Steven Zucker, Metro Denver RLS Support Group Leader

As a member of the RLS Foundation, I eagerly anticipate each new edition of NightWalkers. A few years ago, I would immediately flip to the back pages, checking to see if a Colorado support group had been started. My disappointment eventually led me to inquire about starting one. In April 2019, I was approved to become the Metro Denver RLS Support Group leader.

As I planned for our first meeting, I had several initial goals in mind. I envisioned this group as a source of social-emotional support in our struggles to cope with RLS; a vehicle for educating ourselves as fully as possible regarding RLS symptoms, treatments and ongoing research; and, a way to help one another become effective advocates for our own treatment when visiting doctors and other healthcare practitioners. Feedback from the group suggests that we are upholding these goals.

Our first three support group meetings were held in person. We had ample opportunity to share our stories and compare notes regarding the physicians we see and our treatment regimens. We discussed the remarkable range of medications and treatments used by group members and the ever-changing regimen we all seemed to follow trying to stay one step ahead of our symptoms. Prior to each meeting, I would share a tentative agenda and numerous scholarly articles in hope of facilitating group discussion. The group consistently requested that we invite experts in the field to speak at our meetings. We were very fortunate to have Jacci Bainbridge, PharmD, join our last in-person meeting; her expertise was very much appreciated!

When COVID-19 became our new reality, all in our group were in favor of waiting out COVID until we could resume in-person meetings. But after five months, the group seemed more open to trying virtual meetings. We went from having roughly 25 people attending to only six or seven consistently joining our virtual meetings.

Despite fewer members in attendance, virtual support group meetings have proved successful. Members continued to share successes and frustrations in their attempts to cope effectively with their RLS symptoms. We continued to review pertinent research articles and discussed how to make our time together as valuable as possible and how to eliminate aspects of virtual meetings that were problematic to some. For example, the inability for everyone to speak during the discussion, the lack of opportunity to provide feedback, and various technical issues.

Body language is not nearly as effective when meeting virtually. One big challenge for me as the moderator of the virtual format has been to monitor speaking time and ensure that all members have sufficient opportunity to share and feel truly heard by the group. As members grew more comfortable with the virtual format, conversations among members outside of meetings via email seemed to increase substantially. These email conversations seemed comparable to the naturally occurring in-person conversations during break times, or while leaving our meeting space and packing up food and supplies.

I asked group members for their input regarding the effectiveness of virtual meetings. Many people enjoyed being able to participate in their sweats and especially appreciated eliminating a three-hour drive each way to attend in- person meetings. Here are some additional responses:

One benefit of virtual meetings may be that it allows easier access to speakers and experts in the field. It seems more reasonable to ask for one hour of a speaker’s time online to answer questions than to request that they travel to our meeting site. I hope there is willingness on the part of the experts I contact to participate in this way!

In these times of COVID-induced isolation, it's great to actually see some faces and hear some voices that share common concerns… to pass on and receive encouragement, share experiences with various treatments and medications, and share notes about different doctors. The support of Clara and the Foundation seems to make the virtual meetings go very smoothly.

Meeting and speaking with the group (whether in person or virtually) is something of a comforting balm and gives the additional gift of knowing that we are not crazy, nor are we alone.

When it is safe to meet in person once again, it is my hope that virtual meetings can and will continue. In so many beneficial ways, they are the perfect complement to gathering in person. I trust our group members will agree.

Virtual Support Meetings on Zoom are open to all - RLS Foundation members and non-members, RLS patients and their families, anyone interested in learning more about RLS looking for a safe place to share RLS concerns and victories! To register, go to www.rls.org/VSG.

May 17, 2021

What You Need to Know About COVID-19 Vaccines

By Maddie Lionberger, RLS Foundation Research Coordinator

In March of 2021 the world passed the one-year mark since the coronavirus pandemic was declared a Public Health Emergency of International Concern by the World Health Organization. As of May 17, nearly 34 million cases have been confirmed, with over 600,000 deaths attributed to COVID-19 in the United States alone. Amid the devastation and tragedy, communities and organizations have pulled together in unprecedented ways to overcome the challenges of the pandemic – the development of COVID-19 vaccines is an extraordinary example. Thanks to the concerted efforts of the medical science community, the world has gone from identifying a novel coronavirus to developing safe and effective vaccines in less than 12 months. To add perspective, in the past the fastest vaccine to go from development to deployment took about four years. Unfortunately, misinformation has created a lack of confidence in scientific evidence regarding COVID-19 and about the vaccines designed to fight it.

If you’re on the fence about getting vaccinated, it is important to recognize that anyone of any age can experience severe illness and even death if they contract COVID-19, and certain factors put some groups at greater risk than others. Because people who are age 65 and older are at a higher risk of severe illness from COVID-19, and restless legs syndrome (RLS) is significantly more common among older individuals, it is important for members of the RLS community to review the most up-to-date facts about COVID-19 and vaccines.

The Basics of COVID-19

COVID-19 is caused by coronavirus 2 (SARS-CoV-2). It is predominantly a respiratory illness, but it can also affect other organs. People with COVID-19 experience a wide range of symptoms from mild to severe, including fever, chills, loss of taste or smell, cough, shortness of breath, fatigue, muscle or body aches, headache, sore throat, congestion, runny nose and diarrhea. The incubation period for COVID-19 is estimated to be up to 14 days, with symptoms appearing on average four to five days after exposure. COVID-19 spreads from person to person mainly through the respiratory route; the closer people interact and the longer they interact, the more likely they are to transmit the virus, even if they are not showing symptoms. In a study with a large cohort of 44,000 people with COVID-19, 81% of individuals exhibited mild to moderate symptoms, 14% developed severe symptoms and 5% were reported to be in critical condition. According to the Johns Hopkins Coronavirus Resource Center, the United States is experiencing a 1.8% observed case-fatality ratio, which means the number of deaths for every 100 confirmed cases (almost two deaths per 100 persons infected).

Yet, despite the grim numbers, things appear to be looking up. In mid- February, the director of the Centers for Disease Control and Prevention, Rochelle Walensky, MD, PhD, reported that COVID-19 cases in the US had been in decline for five consecutive weeks. Furthermore, new hospitalizations have consistently gone down since early January. The downward trend is multifactorial, resulting from a combination of behavior changes (masking, social distancing and restricted travel), seasonality, past infections, and vaccinations. To date, three vaccines have been issued Emergency Use Authorization by the US Food and Drug Administration for the prevention of COVID-19. However, the speed at which these vaccines were developed has raised questions in many people’s minds about how they work and how effective they are.

How the Vaccines Work

First, to understand how vaccines work, it helps to look at how the human body fights disease. When pathogens invade the body, the immune system deploys several tools to fight them. Specialized white blood cells recognize foreign substances (antigens) as dangerous and launch an attack on infected cells. Meanwhile, the immune system produces antibodies that allow the body to remember the antigens specific to that disease. Vaccines work by injecting a weakened or inactive virus that triggers an immune response and allows the body to build up a disease-specific memory, so that it’s ready to fight should an infection occur.

The most basic difference among the three vaccines available for COVID-19 has to do with how the vaccine prompts the body to launch an immune response. The Moderna and Pfizer-BioNTech vaccines are both mRNA vaccines, which means that they contain strands of genetic material, called mRNA, that give cells instructions on how to make a harmless version of the protein (the “spike protein”) that is unique to SARS-CoV-2. The immune system recognizes the protein as foreign and builds a defense to fight the antigen specific to COVID- 19. The Johnson & Johnson (J&J) Janssen vaccine is a viral vector vaccine. Instead of using mRNA to provide cells with instructions on how to make the spike protein, vector vaccines contain a harmless adenovirus inserted with DNA genetic material specific to COVID- 19. The DNA then produces mRNA, which causes the same immune response as the Moderna and Pfizer-BioNTech vaccines. Because none of the COVID-19 vaccines contains the live (either weakened or inactivated) virus that causes COVID-19, none of the vaccines can make you sick with COVID-19.

All the vaccines that have received Emergency Use Authorization have been carefully evaluated in clinical trials to ensure that they are safe and effective. The Pfizer and Moderna vaccines have shown astonishing degrees of effectiveness (95% and 94.1%, respectively) in preventing symptomatic COVID-19 infection after two doses of vaccine. The Pfizer and Moderna vaccines require two doses (21 and 28 days after the first shot, respectively). The second dose of the same vaccine is important to ensure that you get robust, long-term protection from COVID-19 soreness at the site of the injection, swelling, body aches, fever, chills, tiredness or headache. Such side effects are normal; they are a sign that your body is building up protection. They are not a sign of infection from COVID-19. Comparing the efficacy of the Pfizer and Moderna vaccines to the efficacy of the J&J vaccine is challenging because of differences in the timing of the trials (the J&J vaccine had to face the more virulent African and British strains, which were not present during the earlier Pfizer and Moderna trials). Overall, across eight countries, the J&J vaccine was shown to be 66% protective (72% in the US) against moderate to severe disease, and 85% effective in protecting against severe disease after a period of at least 28 days.

Another distinction of the J&J vaccine is that it requires only one dose, which has significant public health implications in terms of vaccine distribution. What’s more, the J&J vaccine proved to be 64% effective against moderate to severe or critical disease in South Africa, where coronavirus variants have raised concerns.

COVID-19 Variants

To date, three notable variants of COVID-19 have been documented in the United States and globally: B.1.1.7, B.1.351 and P.1. Virus variants emerge when one or more mutations occur, differentiating the new virus from the wild-type (the term in genetics referring to the typical or predominant form). Mutations can have different characteristics. For instance, these three variants of COVID-19 share a specific mutation that gives them the ability to spread more quickly. It is not surprising that variants have developed, because viruses are constantly evolving; however, the development of variants underscores the importance of keeping up measures that stop the spread of infection and getting the majority of the population vaccinated before more virulent mutations can occur.

Protecting Yourself and Your Loved Ones

As demand for the vaccines has skyrocketed, it has proven difficult for many people to be vaccinated as soon as they would wish, in part because distribution differs from state to state. Many resources are available to help people find vaccine appointments. For example, National Public Radio created a tool in which you can search by your state to find step-by-step instructions as well as tips for signing up and receiving the vaccine. See below for links to this and other resources. In addition to protecting individuals, the goal of wide-spread vaccination is to achieve “herd immunity,” which only happens when enough people in a community are protected because they’ve already had the disease or because they’ve been vaccinated against it. Pass along the helpful, science-based information to your family, friends and neighbors as well. In the meantime, while waiting for your vaccination(s), you can work to stop the spread of COVID-19 by taking four simple actions: 1) Wear a mask, 2) wash your hands, 3) stay at least six feet away from others who don’t live with you, and 4) avoid crowds.

More Information

For the most up-to-date information on COVID-19, visit:

• https://www.cdc.gov/coronavirus
• https://www.npr.org/sections/health- shots/2021/02/18/967448680/how-to-sign-up-for-a-covid-19-vaccine- in-your-state
• https://www.cdc.gov/vaccines/covid-19/reporting/vaccinefinder.html

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.

April 6, 2021

If there is one silver lining that we have seen the restless legs syndrome (RLS) community discover over the course of the COVID-19 pandemic, it is the bonding together of more and more people who are joining our network through online support groups. Since we were forced to “go virtual” as a safety measure, people who had been suffering silently – unable to travel or living too remotely to attend in-person support group gatherings – were suddenly able to share their stories, to give support to some, and to lean on others.

But well before COVID-19 struck, we have been following the journeys of RLS patients in our network. You can read some of their stories on our website and hear from some in our YouTube series “My RLS Journey.”

Caroline’s RLS started when she was in her 30’s and she tells of decades spent trying different remedies and being afflicted with augmentation. Her advice to fellow patients: “Keep an open mind and find the best neurologist you can.” Donnie recalls his journey commencing when he was a teenager. “I didn’t think it was anything out of the ordinary, but it didn’t stop what I was doing so I lived with it.” He acknowledges that RLS affects your life every day, but he didn’t let his RLS deter him from flying gliders and SCUBA diving – things he loves to do.

Each storyteller has charted his or her own unique journey. Lori describes her symptoms as “not pain, but not a tolerable feeling” and says that what helps her cope is, “getting my mind on something other than my legs.” Janice says that the day she first heard about RLS was one of the most memorable in her life: “The day I found out I wasn’t crazy – that I had a disease!”

But what they all share is the realization that they not only needed help themselves, but that they also needed to help others. Donnie says: “The first time I talked to somebody else who had RLS, it gave me some solace, knowing that there are other people out there who know what I’m going through ... so the best thing you can do is, ‘let me help other people, let me help them get through it.’”

Janice agrees that of all the people she’s met over the years, the ones whose stories stick with her are the people who were suffering and who looked to her for advice: “I was so glad I could be one step ahead of them to help them ... and other people have been one step ahead to help me.”

All these journeys are unique. But they all arrive, hand-in-hand, at a common destination – a station-stop on the road to a cure, where caring, hope and compassion meet. There are many ways you can reach this destination, too. You can share your story.

You can participate in an RLS support group. You can help us advocate for RLS research. And you can help the Foundation continue to bring our community together, by donating to the Foundation .

As Janice concludes: “That’s part of the hope, that we’ll all just reach out and grab one another’s hands.”

March 30, 2021

"Congressional Sign On Letter" for Sleep Disorder Research, Education and Awareness

Background

For the third year in a row, an official Congressional Sign On Letter will be sent to the Appropriations Committee asking them to prioritize support for sleep and sleep disorders research and awareness. To be effective, we need your member of the U.S. House of Representatives to "sign on."

Urgent Deadline Approaching

Your Congress Person will only join if YOU (the constituent) ask, and the final deadline is April 8. Take action TODAY, it is imperative! Here’s how:

1. Provide us with your name, address and email here. Include your Representative's name - go to www.house.gov and enter your zip code in "Lookup" to confirm your current member of House of Representatives.
2. Within 24 hours we will return text that you can copy and paste into an email (sample below) along with the email address for the staffer that handles healthcare for your district.
3. Insert staffer's email, cc: clara@rls.org and Press SEND!

Thank you for joining our RLS advocacy efforts by raising your voice for RLS, sleep and sleep disorders!

-----*SAMPLE PERSONALIZED REQUEST EMAIL*-----

To: [first.last]@mail.house.gov
Cc: clara@rls.org
Subject: Sign On Letter – Sleep Community

Dear [Staffer],

My name is [Your Name] and I am a constituent from [City, State]. I am also an advocate for the RLS and sleep disorders patient community. I hope your office will join the attached sign on letter, which supports the community’s appropriations recommendations for FY 2022. To join this letter, please contact Heather Connelly at heather.connelly@mail.house.gov by April 8.

Thank you for your time and for considering this request.

Sincerely,
[Your Name]
[Your Address]
[City, State Zip]

ATTACHMENT: FY22 Sleep Disorders DC and Sign on Letter

Act NOW! Send us your request by April 5!

Please submit your information now, you will receive a personalized email to send to the appropriate health staffer within 24 hours. All requests must arrive before April 5 to meet the email deadline of April 8.

March 5, 2021

Stefan Clemens, an East Carolina University (ECU) associate professor at the Brody School of Medicine’s Department of Physiology, was awarded a US patent for his novel method of treating restless legs syndrome (RLS), which could lead to more effective care over a longer period of time for patients.

RLS is frequently treated with dopaminergic drugs to replace or prevent the loss of dopamine. While these drugs can deliver a high initial effect, they often lose their effectiveness over time and symptoms can worsen, a side effect known as augmentation. Classic RLS treatments act on a dopamine receptor known as D3, which has a suppressive effect in the nervous system.

Clemens’ animal models show that over time the 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, which he received in late August 2020, 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.”

Using a grant from the North Carolina Biotechnology Center, Clemens and a collaborator from the University of Houston will run a small pilot study of the new treatment method. His work also 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 for treating augmentation. “The patent would not have been issued without their help,” said Clemens, who is also working on medical treatments for opioid pain tolerance. “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.” Clemens is a member of the Foundation's Scientific and Medical Advisory Board and is the Chair of the Research Grant committee.

February 26, 2021

Yuqing Li, PhD, 2015 RLS Foundation Grant Recipient, Awarded NIH Funding

The National Advisory Neurological Disorders and Stroke Council (NANDSC), a division of the National Institutes of Health (NIH), awarded a grant to Yuqing Li, PhD, a professor of Neurology and Neuroscience at the University of Florida. Dr. Li and his team will further investigate the genetic mechanisms that are involved in the development of restless legs syndrome.

Dr. Li will build on his previous research concerning the role of the MEIS1 gene in RLS, which was made possible with an RLS Foundation grant he received in 2015. Li’s work involved exploration of an animal model in which he and his team performed a detailed analysis of MEIS1 mutant mice to determine whether they showed RLS symptoms. They also examined the brain’s dopamine system to identify areas affected by the MEIS1 mutation.

“I want to take this opportunity to express my gratitude for the Foundation grant in 2015,” said Li, who published three papers on MEIS1. “The funding allowed us to collect the necessary preliminary data to apply for this NIH grant.”

Li says the Foundation grant allowed him to identify changes in the dopamine and cholinergic systems in the brains of the mutant animals, which suggests that they could be important in causing RLS.

“With the NIH grant award, we are going to develop animal models with MEIS1 altered only in dopaminergic or cholinergic systems,” said Li. “This will allow us to determine the relative importance of the two systems in causing the RLS. We may find out that both systems are important, or one is crucial and leads to the changes in the other. This kind of knowledge will allow us to have a better understanding of how RLS can develop in patients and develop better-targeted therapies for RLS patients.”

The support of the Foundation members has led to the funding of 48 grants totaling over $1.8 million in funding. “The RLS Foundation is excited by the news of this NIH award to Dr. Li. This study will help to expand our knowledge and understanding of the disease leading to development of targeted therapies and, hopefully, a cure,” said Dzienkowski, RLS Foundation executive director. To support the RLS Foundation Research Grant Program go to www.rls.org/donate.