The Search for Biomarkers in PARKINSON’S DISEASE – Part II
The search for a biological marker (biomarker) for the presence of PARKINSON’S DISEASE has been an ongoing and elusive process. Because of the variety of symptoms and their presentations and courses in different times in the disease process, finding one specific and unique identifier of any single symptom is exceedingly difficult. Adding to the difficulty, PARKINSON’S may not be a single disease, marked by a single disease process, but multiple disorders with similar pathologies that have unique differences. But the ability to diagnose accurately early, even before symptoms appear, would enable interventions to improve the quality of life or even to interrupt the progression of the disease. It would also lead to better targets for drug development and then be able to test the efficacy of the new drugs to provide effective treatments for specific symptoms.
The newly developed molecular research tools, proteomics, transcriptomics, metabolomics and genomics are making it possible to develop clinically applicable tests for susceptibility to disease and for diagnosing and following the progression of the disease. These molecular research tools examine biological fluids, such as blood, urine, saliva or cerebral spinal fluid, which for the most part are readily available, easy to obtain and can be processed economically. In the previous article, proteomic research highlighted the study of proteins and peptides and their application to diagnosing and establishing the disease state of the patient with PARKINSON’S DISEASE. Metabolomics is a research process that examines the metabolites, or chemical fingerprints, of various biological cellular processes. It can provide immediate information about the physical state of health on a cellular level. Combined with the information provided by the other “omics” and analyzed with biostatistics and bio information systems, a much more complete picture can be obtained of the state of the organism being observed.
Recent metabolomic studies have looked at the metabolites found in serum in healthy controls and people with PARKINSON’S DISEASE and found subtle distinctions. Such metabolic distinctions could be the result of dietary or personal metabolism processes, but overall, these studies revealed a statistically significant elevation of a metabolite called N-8-acetylspermidine, which appeared to be more prevalent in subjects with more advanced PARKINSON’S symptoms.
A research lab from the Division of Pulmonary, Allergy and Critical Care Medicine at Emory University in Atlanta, proposed to measure the metabolic signatures of slow versus rapidly progressing motor symptoms in PARKINSON’S DISEASE. They used serum samples that were collected from subjects within 3 years of diagnosis as well as from healthy controls. Using dual chromatography-high resolution mass spectromety to analyze the specimens, they found that elevated levels of N8-acetylspermidine were significantly higher in PARKINSON’S subjects that had the more rapidly progressing motor symptoms. Also, the presence of elevated N8-acetylspermidine was present early in the diagnosis and before the symptoms began to progress.
N8-acetylspermidine is a product that is excreted by cells and is found incases of traumatic brain injury or neuroinflamation and neuronal cell death. It is also involved in increasing the production of dopamine. The authors speculate that the increase in N8-acetylspermidine in rapidly progressing form of PARKINSON’S DISEASE, may be an attempt to increase dopamine production in remaining neurons or due to the effects of neuroinflamation.
Because N8-acetylspermidine can be detected early in the course of the disease and before symptoms rapidly escalate, it can serve a biomarker for the progression of the disease, but also may also signal a potential target for a pharmaceutical drug intervention.
Research using the molecular “omics” is still in the early stages, and much more technically complex than this article makes it appear. Knowledge gained from these technologies is progressing rapidly and other labs will be called upon to duplicate and validate these early studies. These are exciting times. Hope for people with PARKINSON’S has never been stronger.
James R Roede, Karan Uppal, Youngja Park, Kichun Lee, Vilinh Tran, Douglas Walker, Frederick H Strobel, Shannon L Rhodes, Beate Ritz, Dean P Jones; Serum metabolomics of slow vs. rapid motor progression Parkinson’s disease: a pilot study.PLoS One 2013 22;8(10):e77629. Epub 2013 Oct 22.
Review by Marcia McCall