By Rebecca Phillips, University Communications science writer

Hill-80PULLMAN, Wash. – An imposter molecule may be misleading doctors who monitor dopamine levels in their patients with Parkinson’s disease.

Washington State University Regents Professor Herbert Hill used a new, high-speed technology to discover a previously unknown compound in the brains of affected rats that looks just like dopamine on standard diagnostic tests.

Dopamine is a neurotransmitter necessary for normal muscle function that decreases in Parkinson’s disease and can be used as both an indicator and treatment for the disease.

The finding suggests that doctors who think they are measuring dopamine levels may actually be measuring levels of its “identical twin.”

The research was done in collaboration with George Stoica at Texas A&M and was recently reported in the publication Analytical Chemistry.

Ion mobility: A race between molecules

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Hill with the electrospray ion mobility equipment. (Photo by Rebecca Phillips, University Communications)

For the study, Hill compared brain tissue from normal and Parkinson’s-like rats using ion mobility–mass spectrometry (IMMS), a process that analyzes both the weight and speed of chemical molecules.

Ion mobility can rapidly identify the chemical makeup of virtually any substance based on the speed of its molecules as they shoot through a test cylinder. Some molecules move fast while others move more slowly providing each with a signature mobility rate.

Hill has been an innovator in the field of ion mobility for nearly 40 years. The technology is used in sensor devices around the world to sniff out illicit drugs, chemical warfare agents and explosives in airports. It also is used in pharmaceutical work and for environmental and space station monitoring.

Mass spectrometry: Weighing in

By combining ion mobility rates with weight readings from a mass spectrometer, Hill can identify molecules in a much more comprehensive way.

“We get a complex array of mass and mobility information that was never before possible,” he said.

All of which led to the discovery of the look-alike dopamine molecule, which weighs the same as true dopamine but travels faster and scores a higher mobility rate.

It also opens the door for an abundance of advances in the medical field.

Mapping the metabolome

Just as scientists before him catalogued the human genome, Hill is helping lay the groundwork for the global mapping of the human metabolome.

Every cell and tissue in the body produces an ever-changing sea of byproducts called metabolites. Researchers like Hill chart metabolites ranging from glucose and amino acids to obscure co-factors in vitamins and enzymes.

He said each metabolite has a unique chemical fingerprint, which can be used to monitor health and the progression of disease states such as depression or cancer.

Conventional methods to measure metabolites have been difficult due to their expense, slow speed and inability to analyze more than a few chemicals at one time.

With IMMS, Hill can measure hundreds of metabolites simultaneously. Within 30 minutes, he detected thousands of compounds from a single drop of blood.

Biomarkers for Parkinson’s

IMMS can also pick out biomarker molecules – abnormal metabolites that indicate disease, infection or exposure to environmental toxins. The aberrant biomarkers stand out like beacons to signify disorders like Parkinson’s disease.

Hill said it can be difficult to diagnose Parkinson’s as there are no specific blood or lab tests that pinpoint the disease. Diagnosis is based mainly on symptoms, medical history and a neurological exam. Finding definitive biomarkers would be a breakthrough.

In the study, Hill and his colleagues found at least nine metabolites that were significantly altered by Parkinson’s disease and may be potential biomarkers.

The dopamine copycat

The major finding was expected – a severe loss of dopamine seen in the affected rats. The surprise was the discovery of the copycat molecule that was not affected.

The twin masks the loss of dopamine, which could, in turn, mislead doctors in their efforts to accurately diagnose and treat patients, Hill said.

Excited with the result, Hill said it “shows us the power of using IMMS – you wouldn’t have noticed the second molecule in any other way.”

Though he thinks the technique will be widely used in the future, it is not presently available for routine clinical diagnoses.

He is collaborating with other scientists to map metabolites for colorectal cancer and diabetes.

Other WSU researchers who participated in the study were graduate students Xing Zhang and Veronica M. Chiu and the late Professor James O. Schenk.

The project was supported in part by funds provided for medical and biological research by the State of Washington Initiative Measure 171.

 

Contacts:
Herbert Hill, WSU Department of Chemistry, 509-335-4657, hhhill@wsu.edu
Rebecca Phillips, WSU University Communications, 509-335-2346, beccap@wsu.edu