Hormonally-Mediated Mechanisms of the Restless Legs Syndrome

THE PROBLEM       
     The restless legs syndrome (RLS) affects between 5% and 10% of adults in industrialized nations. RLS is a neurologic condition consisting of an inexorable urge to move one’s legs at night, often preventing sleep and requiring the unfortunate sufferer to walk/move for between minutes and hours per night to attain relief, during a time when rest and inactivity are most desired. RLS has implications for public health as it is associated with increased incidence of cardiovascular disease, depression, and even mortality. Despite this obvious pertinence to health and well-being, the underlying biological mechanisms of RLS are unknown, limiting the ability to treat, much less cure this troublesome condition.     

THE PROJECT       
     The cause of RLS is unknown and the biology underlying it is poorly understood. The overall purpose of our study is to determine the biological mechanisms underlying RLS. There are several aspects of RLS that suggest that hormones are involved in its biology. Like many hormones, RLS symptoms vary with time of day. RLS occurs commonly with conditions where there exists a hormonally dynamic state, including pregnancy and kidney disease. Also, RLS is treated with medicines that affect the dopamine and opioid systems, both of which have effects on several hormonal axes. Thus we believe that RLS and its symptoms are caused by excessive levels of certain hormones.     
     The hormone alpha-melanocyte stimulating hormone (α-MSH) and its associated melanocortin hormonal axis is an intriguing candidate system, potentially underlying RLS. α-MSH is the main hormone of the melanocortin system and we have demonstrated that when administered to rat produces an RLS-like state, consisting of excessive locomotion, disrupted sleep, and periodic limb movements during sleep. Others have shown that by giving α-MSH, pain hypersensitivity can be produced in the rat, and actually motor restlessness results in the human. These findings are in line with one or more aspects of RLS. Thus, we believe that RLS is caused by excessive amounts of α-MSH.     
     In this project, we plan to measure levels of α-MSH in a large number of persons with RLS and healthy controls. In subjects, we also will study DNA and specific genetic mutations that could result in increased α-MSH levels. Finally, we have requested from NIH brains of persons formerly having RLS and healthy controls without RLS and plan to examine and quantify, in specific brain regions, certain protein receptors which bind α-MSH. This research is currently being conducted at Yale University.  

A CALL FOR HELP       
     The project needs your help. Currently, we are collected preliminary data so that we can present this hypothesis, backed by some data, to NIH in a coherent and compelling way with a goal to procure national funding in order to carry out the work. Preliminary data is costly. We are working with trained research nurses that must get paid. We must also purchase materials for the assay kits to measure α-MSH and its associated protein receptors. No amount is too small to assist us in furthering this important effort, whether it be $50, $100, $500, or $1000, this support is invaluable.      We will use the fund-raised money to pay for the research nursing help, pay for the protein assay kits, pay for the laboratory assistance, pay for kits to isolate DNA, RNA and to make cDNA.

Source: icnw