Parkinson's Disease Research

Our Movement Disorders Program at MUSC is a multidisciplinary program with elements spread throughout the various colleges, departments and divisions of the University. The Murray Center for Research in Parkinson's disease and Related Disorders, which was founded in 2002, enjoys a strong institutional support and has already been successful in raising a significant amount of money through foundations and private donors, as well as through NIH funded projects. This Center is co-administered by Kenneth Bergmann, Dept. Neurosciences, and Ann-Charlotte Granholm, Director Center on Aging at MUSC.

Faculty recruitment in aging related disease at MUSC There is a growing interest in neurodegenerative disease at MUSC, and faculty recruitment in this area has increased significantly during the last 5 years. The funding of healthy aging and age-related diseases increased from 3.5 million dollars in 1996, to more than 15 million dollars in 2003. Hence, there is a significant effort in this area at our institution, in particular as it relates to neurodegenerative disease.

Faculty directly related to movement disorders including Parkinson's disease:

Kenneth Bergmann, M.D., Department of Neurosciences, is the director for the Murray Center for Research on Parkinson's Disease and Related Disorders. He has an extensive movement disorders clinic and collaborates closely with the Center on Aging to expand faculty recruitment and funding in this area.
Istvan Takacs, M.D., Department of Neurosciences, directs the surgical component of the Murray Center for Research in Parkinson's Disease and is the director for the stereotaxic surgery unit of the Department of Neurosciences. Currently, two patients receive a DBS device at MUSC per week. Dr. Takacs also provides research collaboration for a current NIH Grant for functional imaging in patients with deep brain stimulators.
Ann-Charlotte Granholm, Ph.D., Department of Neurosciences, is the Director for the Center on Aging. Her research focus is on animal models of Parkinson's and Alzheimer's disease, related to novel treatment strategies. She collaborates with several Udall Centers (the Univ. Kentucky, Harvard, and Rush Presbyterian/St Luke's Centers) and was the president for the American Society for Neural Transplantation and Repair, ASNTR, last year. She is the PI for our recently submitted PD program project grant, submitted to the National Institutes on Aging.
Mark S. George, M.D., Dept. of Psychiatry, collaborates with both Parkinson's and Alzheimer's research groups at MUSC and has an extensive program related to fMRI and progressive neurodegeneration. As an example of research projects, he is NINDS funded to interleave DBS and fMRI to understand how DBS is acting in the brain to alleviate PD symptoms. This might help understand better ways of programming the DBS generators to increase efficacy, as well as identify other regions for DBS placement. MUSC is a world leader in using Brain Stimulation as a research and clinical tool.
Barbara Tilley, Ph.D., Chair, Department of Biometry, is a nationally and internationally known biostatistician, with ongoing projects in health disparities, design and analysis of clinical trials in Parkinson’s disease and stroke, aging in diverse populations. She is principal investigator of the Statistical Center for the NIH/NINDS funded multicenter Parkinson's disease neuroprotection clinical trial.
Peng Huang, Ph.D., Department of Biometry, has significant experience in both clinical and basic science biometry, and is the director for the Biostatistics Core of a program project related to animal models of Parkinson's disease which was recently submitted to the National Institutes on Aging, NIA. She is currently the principal investigator of the NIH/NINDS funded grant "Global Statistical Tests in Parkinson's Disease Studies", and a biostatistician in an NIH/NINDS funded multi-center Parkinson disease neuroprotection clinical trial (see above).
Yuko Palesch, Ph.D., Department of Biometry, is a biostatistician with many years of experience in the management and analysis of clinical trials. She is an expert in clinical trials in neurological diseases including ALS, stroke, and Parkinson's disease. She is co-principal investigator of the Statistical Center for the NIH/NINDS funded multi-center Parkinson's disease neuroprotection clinical trial.
Jacqueline McGinty, Ph.D., Department of Neurosciences, is the PI of Project 2 in the recently submitted NIA PPG. Her particular strength relates to gene expression in the striatum, using hybridization and microarray techniques.
Narayan Bhat, Ph.D., Department of Neurosciences, investigates the cellular and molecular mechanisms pertaining to central nervous system (CNS) inflammatory response in relation to neurodegenerative diseases. Dr. Bhat, Dr. McGinty, and Dr. Granholm are co-investigators on a recent proposal, funded by the Murray Center, related to minocycline treatment in PD animal models.
Sammanda Ramamoorthy, Ph.D., Dept. of Neurosciences, is the PI for Project 3 in our recently submitted NIA PPG. The research focus is on dopamine transporter mechanisms.
Baerbel Rohrer, Ph.D., Departments of Neurosciences and Opthalmology, is an authority on neurotrophic factors, and the core director for our growth factor (BDNF, trkB, GDNF, and GFRalpha) knockout colonies in our NIA PPG.
Lawrence Middaugh, Ph.D., Department of Psychiatry, has extensive experience in mouse models of movement disorders, in particular as they relate to dopamine deficiencies or depletion. He is the co-director of the program project grant described below.
m. David Morrisette, PhD., College of Health Professions, Rehabilitation Program. His major research area is in motion analysis related to movement disorders.
Esther Forti, R.N., Ph.D., College of Health Professions, Director for the South Carolina Geriatric Education Center (SC-GEC), and also the principal investigator of the Parkinson's disease Outreach and Education initiative, which was recently funded by the Fullerton Foundation (see Program attached to the proposal).

Faculty with an interest in other neurodegenerative diseases:

Mark S. Kindy, Ph.D., Department of Neurosciences, is interested in the molecular basis of disease, specifically, understanding the amyloid formation in Alzheimer's disease and identifying signal transduction pathways in stroke and spinal cord injury. In addition, he is studying Parkinson’s disease in transgenic and MPTP animal models. The primary goal of the laboratory is to determine the underlying mechanisms of these diseases and identify targets and compounds for treatment.
Naren Banik, Ph.D., Dept. of Neurosciences - Research goals have been directed to identification of factor(s), which may be responsible for myelin breakdown in MS and other neurodegenerative diseases.
Jacobo Mintzer, M.D., Dept. Psychiatry. Dr. Mintzer is the principal investigator (and Dr. Granholm the Co-principal investigator) for an Alzheimer Disease Research Center (ADRC) proposal that was submitted to the National Institutes on Aging May 28, 2003. Many of the faculty described in this list are participating investigators in this effort.
Ling Wei, Ph.D., Dept. of Pathology, has a major research interest in the study of embryonic stem (ES) cells that can survive and differentiate after transplantation into the adult brain and can potentially be used to promote repair and restore function in the damaged brain.
Peter Kalivas, Ph.D., Chair, Dept. Neurosciences - Glutamate neurotransmission is thought to contribute to both the degenerative processes and the faulty motor integration occurring in Parkinson's disease. Dr. Kalivas' group are characterizing the role of cystine-glutamate exchange in regulating glutamate transmission, as well as the synthesis of glutathione.
Kumar Sambamurti, Ph.D., Dept. of Neurosciences, has a strong and innovative research program in Alzheimer's disease, in particular related to amyloid formation and cellular distribution. Dr. Sambamurti recently joined us from the Mayo Clinic in Jacksonville.
Inderjit Singh, Ph.D., Dept. of Pediatrics, has a successful research program on neuroinflammatory processes (collaborators include Drs. Banik and Bhat).
Jack Mills, and Judy Dubno, Ph.D., Dept. of Otolaryngology, have a successful research center that focuses on age-related alterations in hearing, including both animal models and clinical studies in a translational fashion.

There are an additional 70 neuroscientists at MUSC that have an interest in neurological disorders that could participate in the successful development of CPP.

Interdisciplinary Organized Research Programs:

The Murray Center for Research in Parkinson's Disease and Related Disorders - This research center is administered through the Department of Neurology and the Center on Aging and can be characterized as a multidisciplinary center with a translational approach, focusing on movement disorders.
Parkinson's Outreach and Education Training Program - This is a recently funded program (Fullerton Foundation) that aims to provide training and outreach to health care providers, patients with Parkinson's diesase, and their caregivers in South Carolina. It is administered through the SC Geriatric Education Center and the Center on Aging.
Autonomic Function Laboratory (AFL) Directed by Kenneth J. Bergmann, M.D., Department of Neurology - Autonomic dysfunction is a cardinal sign of many Parkinson syndromes and a major source of morbidity in this population. It is a diagnostic criterion in both Diffuse Lewy Body Disease and Multiple System Atrophy. MUSC has one of the few comprehensive laboratories in the US and is currently undergoing a software upgrade and adding the ability to quantify dermal cholinergic function. The AFL has been fully functional for the past two years.
Cognitive Testing Laboratory Directed by Mark T. Wagner, PhD, Department of Neurology, Division of Neuropsychology - Dr. Wagner and his staff determine the cognitive capabilities of this population, a function necessary for the definitive diagnosis of Parkinson syndromes. He is critical to the development of new testing techniques, which define the anatomic substrate of cognitive dysfunction in movement disorders, and works closely with the functional imaging projects.
Parkinson Disease Neuroprotection Statistical Center - This Statistical Center (U01NS043127) is funded by NINDS to work with the Clinical Coordinating Center in Rochester, NY. The Statistical Center (PI: Dr. Tilley) will provide analyses, monitoring, and statistical methodological development related to a large sample trial of neuroprotective agents to be conducted for patients with Parkinson’s disease. The Statistical Core is also charged with helping to facilitate the recruitment of minority participants into the large sample trial and evaluating instruments and approaches used to study neuroprotection in diverse populations.
Center for Advanced Imaging Research Functional MRI Imaging Director: Mark George, MD, Departments of Psychiatry, Neurology and Radiology & Positron Emission Tomography Director: Kenneth Spicer, MD, PhD, Department of Radiology - The ability to image the nervous system with regard to normal and abnormal physiological activity is uniquely developed at MUSC. It is rare to have the capacity of both fMRI and PET scanning in a single institution. The laboratories are already participating in NIH-funded studies related to aspects of Parkinson’s disease, such as the DBS study mentioned above (see Dr. George). The fMRI Laboratory has recently acquired a 3.0 Testla coil magnetic resonance imager and this will enable us to perform studies at the very best levels of temporal and spatial resolution.
The Center on Aging - The Center on Aging is a research, service, and education center at MUSC. The center was approved by the South Carolina Commission on Higher Education December 3, 1987, giving it the status of the oldest research center at the University. The vision is to enhance the quality of life for older residents of South Carolina through research, education, and outreach on healthy aging and age-related disease. The Alzheimer's disease research program (ADRC, PI: Mintzer, Co-PI: Granholm) as well as the program project on Parkinson's disease animal models (PI: Granholm) are administered through the Center on Aging. This fiscal year we raised more than $600,000 for Parkinson's disease research in collaboration with Dr. Bergmann.
Neuroscience Institute - the Institute has become a nucleus of academic excellence, and has contributed to attracting out-of-state businesses to Charleston, as well as distinguished experts and private and federal funding to support its research. Each year, millions of people die or are disabled by neurological and psychiatric diseases. High quality, intensive research is our best hope for discovering why. The MUSC Neuroscience Institute is at the forefront of this research, and is working diligently to bring new hope and understanding to patients devastated by neurological diseases.
Alzheimer’s Research and Clinical Programs - The MUSC-ARCP program was developed by MUSC Geriatric Psychiatry and the Department of Neurosciences to serve as a statewide resource for patients, families and physicians. The program provides access to comprehensive inpatient and outpatient diagnostic and treatment services, clinical drug trials and other types of research studies and educational opportunities.
Determinants of dopamine neurons during aging and Parkinson's Disease - This collaborative research program is a collaboration between several different departments (Neurosciences, Psychiatry, and Opthalmology) in the College of Medicine. We are developing a novel animal model for Parkinson's disease, using aged animals that are heterozygous to a growth factor deletion (GDNF or BDNF). The program has resulted in one RO1 and one PO1 proposal so far, administered from the Center on Aging (overview submitted as an Appendix).

Clinical Research capabilities, patient populations, registries and bioinformatics resources:

The Movement Disorders Clinical Program - Dr. Kenneth Bergmann (Neurologist) currently sees over 700 Parkinson’s patients on a yearly basis and this number will increase with the addition of a second neurologist who will mainly focus on Parkinson’s disease (see details regarding the clinical program above). The Movement Disorders Program has recruited a new Director, Vanessa Hinson, PhD, MD who will be started at MUSC in August 2003. Clinical Core facilities in various departments and divisions of MUSC provide interdisciplinary collaborative efforts, including neurology, neurosurgery, psychiatry, neuroradiology, neuropathology, neurophysiology, and neuropsychology, physical medicine and rehabilitation, pharmaceutics, biometry and epidemiology, and environmental sciences, among others. The program includes a clinic facility for outpatient care, relevant clinical laboratories, and an outpatient clinical investigations division (see enclosed detailed program). The clinical program also provides specialized clinical research experiences for medical students, Neurology and Psychiatry residents in the College of Medicine.
Movement Disorders Program Registry - The Movement Disorders Program at MUSC has established a Registry of individuals with Parkinson’s disease that include over 700 patients. All patients in the Movement Disorders Program are entered into a relational database specifically designed for Parkinson’s disease, clinical and research data entry, and clinical research patient selection. It is fully supported by our computer service department and has been operational for the past year. Links to the entire medical university hospital inpatient database are being developed using an HL7 protocol.
Intraoperative neurophysiology laboratory. Co-Directors: Kenneth J. Bergmann, MD, Department of Neurology and Istvan Takacs, MD, Department of Neurosurgery. Acquisition of state-of-the-art instruments (the Axon Guideline amplifier and microdrive system) has allowed the University to become one of a handful of centers that can perform microelectrode recording guided stereotactic functional neurosurgery for movement disorders. Under the guidance of Istvan Takacs, MD, a pioneer in the implementation of deep brain stimulators in the US, the interventional neurosurgical program has rapidly become one of the most productive programs in the US, performing two bilateral subthalamic nucleus deep brain stimulation cases weekly, among other types of functional neurosurgery. The surgical procedures offered for the treatment of PD include thalamotomy, pallidotomy, and deep brain stimulation.
SC Cooperative for Healthy Aging in Minority Populations - is one of six NIA funded Resource Centers on Minority Aging (RCMAR). This Center , affiliated with the MUSC Center on Aging, provides support to investigators at MUSC and across South Carolina who are interested in diseases affecting older underrepresented minorities with a particular focus on African Americans. Center support includes assistance in developing or assessing measurement tools as applied to this older population. The Cure Parkinson Program would have access to the resources of this Center should they be needed. The RCMAR also identifies and mentors new minority investigators and would be able to identify potential new minority investigators to engage in the Cure Parkinson's Program.
Memory Disorder Clinic - As a joint program between the Department of Neurology and the Alzheimer’s Research and Clinical Programs, this clinic provides a comprehensive approach to the assessment of patients with memory problems. A behavioral neurologist or neuropsychiatrist with experience aids in the diagnosis and management of dementia evaluates patients. The evaluation also includes a social and functional assessment.
The Clinical Information Group (TCIG) - The Clinical Innovation Group was formed by the Medical University of South Carolina Foundation for Research Development in an effort to align the goals of scientific clinical research and fiscally responsible healthcare provision. TCIG provides: project design/protocol development, project management, data management, central randomization, regulatory compliance / FDA interface, site / participant recruitment, central laboratory, biostatistics, epidemiology, and clinical economics, reporting and publications, international coordination capabilities

Participation in management of intellectual properties:

Robert I. Pozner, Ph.D., Director, Foundation for Research Development - The MUSC Foundation for Research Development (MUSC FRD) is a 501c3 organization affiliated with MUSC. It was created in 1996 to carry out technology transfer, new business development, multisite clinical trial management, and economic development activities on behalf of MUSC. Its staff includes individuals with technology evaluation, licensing, business development, accounting, legal, and all aspects of clinical trial management expertise necessary to accomplish the functions described above.

With respect to the CPP, MUSC FRD is prepared to participate in technology transfer, new business development, and clinical trial management as they pertain to Parkinson's disease. Further, we are prepared to review our intellectual property portfolio for relevant technology and to share information concerning future research and inventions related to Parkinson's disease with CPP participants.

Other programmatic aspects:

Motion Capture - In collaboration with the Charleston Film Studios, we are developing a novel motion capture program that will allow real-time human or animal motions to be translated into numerical data streams that can be attached to 3-dimensional data bases. The numerical data can be charted and graphed for analysis at any time after capture, as well as being exportable to other software applications. The "Heather" Motion Capture program is innovative and may allow us to analyze motion in a capacity of up to 900 measurements/sec in real time, which we intend to develop for both human and animal model use (see attached program). This Hollywood film company, which is relocating to Charleston, also has tremendous data storage and analysis capacity, and will bring networking capabilities to Charleston of the highest speed and capacity (they usually record from 6 film sites simultaneously in real-time).
Molecular Therapeutics, Inc. - Drug testing in animal models, development of animal models, development of drugs for neurodegenerative and cardiovascular diseases.
Argolyn, Inc. - Their proprietary chemistry platform makes biologically active peptides intrinsically more “drug-like." The technology does not employ extrinsic packaging systems, delivery molecule, or leader sequence. Instead, the technology is applied at the amino acid level resulting in improved stability, increased penetration across biological barriers, and enhanced selectivity within receptor families.
GenPhar, Inc. - A biopharmaceutical company dedicated to becoming a leader in viral diagnostics, vaccines, and cancer therapy. They utilize technologies at the forefront of molecular bioengineering, developing new products that will assist physicians and benefit patients in the ongoing efforts to control important viral diseases and cancers.

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