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.