Monday, October 22, 2012

Translational Research: From Bench To Bedside

Robert Lipsky
Robert Lipsky, Ph. D
          Have you ever taken a medication when you were not feeling well? How do we know it's effective against illnesses? What allowed it to go from the laboratory research setting to your medical cabinet?

          On October 18th, 2012 at George Mason University, my NEUR410 class attended a presentation lecture conducted by Robert H. Lipsky Ph. D, the Director of Translational Research in the Department of Neurosciences from Inova Fairfax Hospital. He discussed various topics relating to his translational research including warfarin (coumadin), clinical depression, and spinal cord injuries.


          What is translational research? Dr. Lipsky defined it as taking findings in basic research and rapidly moving them to medical applications to produce meaningful health outcomes, "bench to bedside."
Translational Research diagram
Warfarin chemical structure
          The drug warfarin is commonly used to prevent the formation of blood clots. Although it is a relatively safe treatment, warfarin affects individuals differently and in some cases may cause life threatening side effects such as a hemorrhagic stroke. This is known as pharmacogenetics, when an individuals' genetic differences of metabolic pathways affects their responses to drugs during both therapeutic and adverse effects. Dr. Lipsky suggested that individuals carrying a variation in the vitamin K epoxide reductase complex (VKORC1) gene and/or cytochrome P450 CYP2C9 gene will respond differently to warfarin. Those genes have a complex-dose relationship with warfarin and will affect the response of the drug on individuals who carry it. The VKORC1 and CYP2C9 genotype accounts for about 50 percent of the variation in response to warfarin thus acting as a biomarker for determining initial dose. If individuals are good drug metabolisers, they will be at a low risk of hemorrhage and if they are poor drug metabolisers, they will be at a higher risk. Those individuals must be monitored closely or not given warfarin at all. The approach Dr. Lipsky suggested was to start individuals at risk in a small dose and monitor their side effects while slowly increase their doses over time if they are able to tolerate it.

VKORC1, CYP2C9, and warfarin interaction
          Major Depressive Disorder (MDD), commonly known as clinical depression is one of the greatest problems and killers throughout history. It affects approximately 18.8 million American adults and the rate of clinically depressed children is increasing drastically. During a twin study, Dr. Lipsky stated 40-50 percent of MDD are gained through heredity. Other potential environmental risk factors include chilhood abuse and stressful life events, such as alcohol. Further studies on the occurrence of neuropsychiatric disorders in monozygotic and dizygotic twins showed the following being having the highest to lowest genetic impact on MDD: Huntington's disease, schizophrenia, alcoholism, social phobia, panic disorder, anxiety disorder, and neurotism. 
"I am now the most miserable man living... 
I must die or be better." -Abraham Lincoln, 
suffered life-long depression.
          As treatment for these conditions, Citlopram, an antidepressant from the selective serotonin reuptake inhibitor (SSRI) class, was administered. When that did not work, what happens then? Dr. Lipsky discussed the Sequenced Treatment Alternatives to Relieve Depression (STAR*D)Project, which tested individuals' serotonin transporter, specifically HTTLPR. The results concluded showed nothing that predicted a cure or response. However, it did suggest that individuals who were "poor responders" and expressed low serotonin transporter levels had S and Long G alleles.


Oscillating Field Stimulation (OFS) Device
        
          Dr. Lipsky also discussed the importance of researching new treatments for spinal cord injuries (SCI). SCI affects 250,000 Americans, 52 percent of which are considered paraplegic and 47 percent quadriplegic. 11,000 new injuries occur each year and 56 percent of it affects the ages between 16 and 30. The few treatments for SCI today include medications, immobilization techniques, and surgery. Because little progress have been made treating SCI, Dr. Lipsky has requested a grant to continue research on Oscillating Field Stimulation (OFS) Device.
         
Cover Image
Oscillating Field Stimulation (OFS) Device
          OFS is a device placed in an individual that sends an electrical current to the injured spinal cord to prevent the "die back" phenomenon of several neural pathways. It regenerates the spinal cord and promotes healing directed to neurological recovery. Although very little research has been done on OFS, data from the small study group that was collected showed tremendous improvement compared to the control group. After 15 weeks following implant, OFS improved sensation in complete SCI patients. This was measured by a pin prick and light touch. Other improved symptoms include improved bladder and bowel control, sex life, no UTI, and overall better physical therapy and rehabilitation outcomes. Despite the positive signs from this research, nothing is currently being done to further investigate OFS. The major roadblock is money because conducting more experiments like this will cost over several million dollars each.

          Translational research facilitates the process of basic science findings to practical application that ultimately enhance human health and well-being. The topics discussed above were just a few examples of this type of research. It is the driving force that translates laboratory findings to meaningful health outcomes. Dr. Lipsky's presentation on his research demonstrated the pros and cons of translational research. The major roadblock he and others face is, of course, money. His research on warfarin got us one step closer to understanding how the drug impacts different individuals depending on their genotypes. The new acquired knowledge of being able to identify some people who are more susceptible to serious side effects that others is a great accomplishment. The same goes for his findings regarding MDD and the S and Long G alleles. The most interesting part of his presentation, to me, was OFS and it's ability to alleviate acute SCI so effectively. I would like to see Dr. Lipsky succeed to receive a grant that will permit him to continue research in this field because it will be greatly beneficial to the millions suffering from SCI with no current effective treatment. It is because of the efforts of Dr. Lipsky and other scientists that transitional research will discover new scientific breakthroughs in the laboratory and apply it in the practical setting that will ultimately drive the human race forward.






References (images)

http://neuroscience.gmu.edu/system/person_images/1452/cropped/Robert-Lipsky.jpg?1305916700
http://www.umcutrecht.nl/NR/rdonlyres/EB1B29D9-F623-4245-B262-D79B7904D980/4902/transaltional3.jpg
http://www.medicalisotopes.com/structures/11072.png
http://ars.els-cdn.com/content/image/1-s2.0-S0049384806004373-gr1.jpg
http://upload.wikimedia.org/wikipedia/commons/f/fe/Abraham_Lincoln_seated,_Feb_9,_1864.jpg
http://www.healingtherapies.info/OFS.jpg
http://www.sci-info-pages.com/facts.html


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