Funded Research

2019 RLS Research Grant was awarded to:


Sergi Ferré, MD, PhD

Serge Ferre

Dr. Ferré will explore how opioid medications work in the brain to relieve RLS symptoms. This research builds on several Foundation-funded studies previously conducted by Dr. Ferré, who is a member of the RLS Foundation Scientific and Medical Advisory Board.

Dopamine agonists, alpha-2 delta agents and opioids are highly effective in treating RLS, Dr. Ferré seeks to understand the biologic elements that may be common to these three classes of drugs that makes them so effective in treating RLS, thus opening the door for future drug development.

Opioid medications act on three types of opioid receptors in the brain. One of these – the mu opioid receptor – is the target of the opioid medications, such as methadone, that are a very effective treatment for severe RLS when used in low total daily doses. RLS is a neurological disease that has a distinctly different underlying neuropathology than that associated with typical pain syndromes.

In the current study, “Elucidating the mechanisms of the therapeutic effects of opioids in RLS,” Dr. Ferré’s team aims to identify the locations of mu opioid receptors involved in improving RLS symptoms with opioids. With this information, they hope to determine if specific opioid medications could selectively act on these mu opioid receptors, reducing the risk of unwanted side effects.

2017 RLS Research Grants were awarded to:

John Winkelman, MD, PhD

John Winkelmann

The RLS Foundation has awarded a $144,000 grant to John Winkelman, MD, PhD, of Harvard Medical School/Massachusetts General Hospital, for a pilot study on the use of opioids to treat RLS. The two-year project is part of broader research to establish the long-term safety and effectiveness of opioids for treating the disease.

In the study, Dr. Winkelman and his team will recruit 200 patients from across the US who are taking opioids for RLS. The team will collect data on opiate medication and dose, severity of RLS symptoms, opiate side effects, sleep quality and augmentation. The first two years of data collection, supported by the RLS Foundation grant, will establish the parameters for ongoing, long-term research and enable the team to apply for further funding for this work.


William Ondo, MD

Dr. William Ondo

The RLS Foundation has awarded a $37,000 grant to Dr. William G. Ondo of Houston Methodist Neurological Institute to study a new medicine to treat RLS patients who have augmentation.

"Augmentation is a condition where RLS symptoms start to worsen after initially improving, while on dopamine agonist treatments such as pramipexole, ropinirole, Neupro, and levodopa. Since most patients with an urge to move initially respond to properly dosed dopaminergic medicines, augmentation is arguably the biggest practical impediment to successful chronic management of RLS" explains Ondo. "The exact mechanism of augmentation is not known, however, based on animal studies we performed, we hypothesize that it is caused by increased activity of dopamine type I (D1) receptors. In animal models these receptors in the spinal cord increased when mice models of RLS were chronically treated with typical dopamine drugs, specifically pramipexole. Dopamine type I receptors have many features which are the exact opposite of dopamine type 2 (D2) and 3 (D3) receptors in the spinal cord. The dopamine medicines still stimulate these D1 and the D2/D3 receptors, which we feel results in the contradictory effect that they both improve and worsen RLS at the same time."

"We have identified an investigational drug which blocks D1 receptors without blocking D2 and D3 receptors, ecopipam. In this small trial, we will administer this drug in a blinded manner to patients already on dopamine medications who have augmentation, to see if it can reverse the augmentation and improve their symptoms."


2016 RLS Research Grants were awarded to:

William Padula, PhD, MS, MSc


The first in 2016, a $36,750 grant was awarded to William Padula, PhD, MS, MSc, of the Johns Hopkins Bloomberg School of Public Health, for a research study to assess the economic burden of RLS over the lifetime of the disease. This study will evaluate the direct and indirect costs of RLS diagnosis and treatment, as well as costs related to loss of work and time by individuals living with RLS. Findings will potentially help increase future RLS research funding from agencies such as the National Institutes of Health (NIH).

2015 RLS Research Grants were awarded to:

Yuqing Li, PhD


Dr. Li will continue his research on the role of the MEIS1 gene in RLS. In this study, called “Characterization of MEIS1 heterozygous knockout mice as a model of Willis-Ekbom disease,” the researchers will perform a detailed analysis of MEIS1 mutant mice. They will look at whether the MEIS1 mutant mice show other RLS symptoms such as changes in sensation.

They will also examine the brain’s dopamine system and determine what areas are affected by the MEIS1 mutation. Dr. Li's group will try to treat a group of MEIS1 mutant mice with known dopamine drugs used in RLS patients to see whether these drugs alleviate the RLS symptoms in these mice. The goal is to validate the MEIS1 mutant mice as a useful model for testing other potential treatments for RLS.

Sergi Ferré, MD, PhD

Serge Ferre

Dr. Ferrés research will explore cortico-striatal transmission in iron-deficient rats as a model for screening of drugs potentially useful in treatment of restless legs syndrome.

There are multiple potential medications that for theoretical reasons should be considered beneficial for RLS, but many of these are not available for human use and, for those that are available, testing them in RLS patients would be expensive and time consuming. Efficient drug screening is needed to select drugs that seem promising for RLS, which could then be studied in RLS patients. This project aims at obtaining a new animal model for such screening.

The first goal of the project is to demonstrate that iron deficiency in rats is associated with increased cortico-striatal glutamatergic transmission. The second goal will be validating our model by demonstrating the ability of drugs already known to be efficient in RLS patients to revert the changes induced by iron deficiency on cortico-striatal neurotransmission in rats. The model would then be used to screen new compounds that could potentially be potent modulators of cortico-striatal neurotransmission.