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Iron Transporters Implicated in Restless Legs Syndrome: Presented at SFN

By Roberta Friedman, PhD

NEW ORLEANS, LA -- November 14, 2003 -- Problems with a transporter protein that ferries iron in neurons may be responsible for Restless Legs Syndrome, a condition that interrupts sleep, according to research reported here November 11^th at the Society for Neuroscience 33^rd Annual Meeting.

In diabetes, cells starve because the insulin needed to bring fuel into the cells is missing. Similarly, Restless Legs Syndrome appears to be a defect in getting iron to the neurons that need it.

"We conclude that Restless Legs Syndrome is caused by iron deficiency," said study investigator Xinsheng Wang, MD, PhD, postdoctoral fellow, department of neural and behavioral science, Penn State University, Hershey, Pennsylvania, United States. The iron deficiency may stem from a defect in the TRP 1 protein.

Critical neurons in the substantia nigra, the tiny brain region responsible for much of the brain's dopamine, apparently lack an iron-transporter protein in people with Restless Legs Syndrome. Levels of the IRP 1 protein were decreased in neuromelanin cells culled from the substantia nigra, for 4 patients with the syndrome, compared with those from 4 people without the condition. Investigators took the cells from the brains by Laser Capture Microdissection.

A protein called Thy1, on the surface of cells in the substantia nigra, helps release dopamine. Thy1 requires iron to work properly. On histology, Thy1 declined in the autopsy brain samples from the 4 people with the syndrome, compared to people without the condition.

The syndrome keeps people awake at night with an urge to keep moving their legs. Treatment has consisted of iron supplements, and also dopamine-boosting agents.

The simple explanation that iron can't get to these neurons shows why the empirical treatment has worked, but has also proved a delicate balancing act for clinicians. Iron overload can cause hemochromocytosis in the patients. Dopamine agents also can stop working, and can eventually make the situation worse.

Dr. Wang agreed that the findings can explain the reasons for and the difficulties with existing therapy. He added that this discovery "sooner or later will help people [with Restless Legs Syndrome]."


[Study titles: Thy1 is decreased in Restless Legs Syndrome: Further evidence for an iron-dopamine connection. Abstract 735.2; Study title: Misregulation of iron in neuromelanin cells in Restless Legs Syndrome. Abstract 735.3]

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