New Approach to Treat Augmentation

The RLS Foundation's Scientific and Medical Advisory Board (SMAB) recently approved funding for a research proposal by Dr. William Ondo of Houston Methodist Neurological Institute, an RLS Quality Care Center.

After a rigorous selection process, the committee approved Dr. Ondo's grant for Foundation funding for a research study. Dr. Ondo explains:

"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.

"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."

Dr. Ondo serves as director of the Movement Disorder Clinic at the Houston Methodist Neurological Institute. Throughout his career, Dr. Ondo has written more than 250 articles and book chapters. A movement disorder specialist, he is board certified in adult neurology and sleep medicine. Dr. Ondo's research specializes in Parkinson's disease, essential tremors, the use of botulinum toxins in treating movement disorders, and restless legs syndrome. At the RLS Foundation, Dr. Ondo is an active member of the SMAB Opiates Committee.

“Dr. Ondo’s proposal presents an exciting opportunity to investigate a new approach to treat RLS augmentation," says RLS Foundation Executive Director Karla Dzienkowski. "As the only organization with a dedicated RLS Research Grant Program, it is our hope that research like Dr. Ondo’s will lead to new and better treatments and one day, a cure for patients living with RLS.”

Since its inception in 1997, The RLS Foundation's research grant program has funded nearly $1.6 million in competitive research grants for the study of restless legs syndrome. In 2016, the Foundation committed to develop this program even further by:

• Increasing research funding to $200,000 annually for up to eight pilot grants
• Accepting grant proposals on a continual basis, rather than just once per year, using a rigorous NIH review to evaluate grant proposals
• Providing counsel to RLS Foundation grant seekers to improve the strength and outcomes of their research studies
• Identifying potential sources (NIH) of later-stage funding for grantees
• Expanding the reach to biotech and medical technology companies as collaborators that can help achieve progress toward a cure

Interested in applying for a research grant on RLS? Read about the guidelines and application here.