Emerging Subspecialties in Neurology: Translational research in movement disorders
Sheng-Han Kuo, MD and
George R. Jackson, MD, PhD
From the Department of Neurology (S.-H.K.), Baylor College of Medicine, Houston, TX; and Department of Neurology (G.R.J.), University of Texas Medical Branch, Galveston.
Address correspondence and reprint requests to Dr. Sheng-Han Kuo, Department of Neurology, Columbia University, 710 W. 168th Street, 3rd floor, New York, NY 10032 sk3295{at}columbia.edu
Movement disorders constitute a unique field and several characteristicsdistinguish it from other subspecialties of neurology. Movementdisorders specialists rely on clinical phenomenology to generatedifferential diagnoses and based on a detailed history and neurologicexamination, an accurate clinical diagnosis is usually made.Although the pathogenesis of many disorders in the field isnot well-understood, therapeutic measures have been developednot only for patient care but also for the exploration of humanneuroscience. For example, levodopa use in Parkinson disease(PD) confirms the critical role of dopamine in the disease pathogenesisand deep brain stimulation leads to a better understanding ofbasal ganglia circuits. These powerful tools provide insightsinto diseases and also help to illuminate mechanisms of humanmotor control. In addition, most of the movement disorders clinicalpractice is outpatient based, and few emergencies exist in thissubspecialty, making it an ideal career option for those neurologistsseeking to integrate research activities with clinical practice.Historically, many movement disorders specialists have conductedeither basic science or clinical research and have made majorprogress in the field.
Translational research is defined as "the transfer of new understandingsof disease mechanisms gained in the laboratory into the developmentof new methods for diagnosis, therapy, and prevention and theirfirst testing in humans."1 Translational research in movementdisorders can mainly be divided into 3 domains: basic scienceresearch, human motor control, and clinical trials. The basicscience aspect involves studying human diseases in animal modelsby genetic engineering or by pharmacologic manipulation to furtherunderstand the disease process or to carry out drug screening.Human motor control studies utilize electrophysiologic or imagingtools such as transcranial magnetic stimulation and functionalMRI to explore the human neural circuits for movements. Theclinical domain of translational research aims to apply thenew therapies to human subjects. Several examples demonstratethe success of rapid translation from the bench to bedside.Viral vector mediated growth factor delivery was proven successfulin the rat model of PD in the late 1990s and it was recentlytested in human subjects with an exciting phase I result.2 Thestudies on the monkey pedunculopontine nuclei in motor controleventually led to the potential new targets for deep brain stimulationfor the treatment of PD.3
Fellowship training in translational research.
Clinical movement disorders fellowships are currently not accreditedby the Accreditation Council for Graduate Medical Educationor the United Council for Neurologic Subspecialties. Therefore,there is no standard core curriculum. The clinical movementdisorders fellowship training at Columbia University can bean example for the training curriculum design.4 For physician-scientistswho are interested in pursuing training in translational researchin movement disorders, a balance between clinical practice andresearch activity is essential and can be integrated in severaldifferent ways. For example, one can complete 1 to 2 years strictclinical training before going on to laboratory-based or clinicalresearch training. Alternatively, a trainee can spend 1 dayor 1/2 day of the week in the clinic and devote the rest ofthe time to research activities over the course of several years.Each fellowship program has different requirements and focuseson different domains of translational research. Therefore, applicantsshould consider many factors in each individual training program.The funding for translational research fellowships often comeseither from clinical programs or from research funding. A traineecan also learn grant-writing skills to prepare for a futureacademic career. The K award series is a mentored career developmentaward provided by the NIH to support young investigators workingwith mentors to achieve successful research careers (http://grants.nih.gov/training/careerdevelopmentawards.htm).Other private foundations such as the PD Foundation also provideclinician-scientist training opportunities (http://www.pdf.org/en/grantfunding).Despite the decreasing funding from NIH for PD and the stablefunding for dystonia and Huntington disease research in thepast 5 years (http://www.nih.gov/news/fundingresearchareas.htm),NIH has made translational research a priority and 24 Clinicaland Translational Science Award programs have been establishedin academic centers. It is expected that by 2012, NIH will havea $500 million budget for translational research.1 Thus, amplepotential exists to develop a physician-scientist career intranslational research.
Key features of successful translational research career development.
Several components are keys to developing a career in translationalresearch. A trainee works with clinical movement disorders expertsto gain clinical experience as well as with translational sciencementors to develop research interests. Good mentorship for bothclinical and research training are essential.5 A good balancebetween clinical practice and research activity is also a keycomponent. Furthermore, it is also important to seek a supportiveenvironment with a good track record for training successfulphysician-scientists. Several academic neurology departmentsin the United States have a long history of training physician-scientistsand have integrated programs designed specifically for thispurpose.
Translational research training in movement disorders providesan ideal platform for clinical, scientific, and potential grantwriting experience. An academic career in translational researchcan be very rewarding with the integration of direct investigationof disease process, discovery of new therapies, and advancementof science. Some of the principles in translational researchtraining can also be applied to other subspecialties in neurology.New diagnostic tools and therapeutic measures are rapidly developedand tested on human subjects. Cell transplantation has beentested on patients with PD and Huntington disease. Deep brainstimulation has now been applied more widely to various disordersincluding medically refractory Tourette syndrome and depression.The ample funding opportunities provided by NIH and PD Foundationencourage young physician-scientists to develop careers in thefield. The future of translational research in movement disordersholds promise and offers exciting opportunities to understandhuman motor control and to advance the treatment of diseases.
Dr. Kuo serves as an editorial team member for the Residentand Fellow Section of Neurology reg;. Dr. Jackson serves onthe scientific advisory board of the American Foundation forAging Research; serves as an editorial board member of the InternationalJournal of Developmental Neuroscience; and receives researchsupport from the NIH [NIH/NINDS/NIA #R01 NS046489 (PI), NIH/NIA#P50 AG16570 (Subproject PI), NIH/NIEHS #P50 (Subinvestigator),and NIH/NIEHS #R01 ES01574 (Subinvestigator)].
Disclosure: Author disclosures are provided at the end of thearticle.
Woolf SH. The meaning of translational research and why it matters. JAMA 2008;9:299:211–213.[Free Full Text]
Marks WJ, Jr., Ostrem JL, Verhagen L, et al. Safety and tolerability of intraputaminal delivery of CERE-120 (adeno-associated virus serotype 2-neurturin) to patients with idiopathic Parkinson's disease: an open-label, phase I trial. Lancet Neurol 2008;7:400–408.[Medline]
Stefani A, Lozano AM, Peppe A, et al. Bilateral deep brain stimulation of the pedunculopontine and subthalamic nuclei in severe Parkinson's disease. Brain 2007;130:1596–1607.[Abstract/Free Full Text]
Portera-Cailliau C, Victor D, Frucht S, Fahn S. Movement disorders fellowship training program at Columbia University Medical Center in 2001–2002. Mov Disord 2006;21:479–485.[Medline]
Lee A, Dennis C, Campbell P. Nature's guide for mentors. Nature 2007;447:791–797.[Medline]
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