Stanley H. Appel, M.D.
A.B. Harvard University
Intern in Medicine, Massachusetts General Hospital, Boston, MA
Stanley H. Appel, M.D. is the Peggy and Gary Edwards Distinguished Endowed Chair for the Treatment and Research of ALS, Department of Neurology, Neurological Institute, The Methodist Hospital and Professor of Neurology at Weill Medical College of Cornell University. He was previously Chair of the Department of Neurology at Baylor College of Medicine as well as Chief of the Neurology division and the James B. Duke Professor of Medicine at Duke University Medical Center, North Carolina. Dr. Appel is a native of Massachusetts and received his Bachelor Degree at Harvard University and his Medical Degree from Columbia College of Physicians and Surgeons. He is Director of the MDA/ALS Research and Clinical Center at the Methodist Neurological Institute, and past Director of a National Institute of Aging Alzheimer’s Disease Research Center.
Dr. Appel is a member of numerous professional societies and committees, and is the author of 15 published books and over 350 articles on topics such as ALS, neuromuscular disease, Alzheimer’s Disease, and Parkinson’s Disease. He has received a number of awards for his accomplishments in Neurology and Biochemistry, including the Gold Medal Award in 1997 from Columbia College of Physicians and Surgeons for “Distinguished Achievements in Medicine”, the Sheila Essey Award in 2003 from the American Academy of Neurology for “outstanding research in Amyotrophic Lateral Sclerosis”, Elected Fellow of the American Association for the Advancement of Science in recognition of the “dedication and commitment to advancing science and serving society” in 2003, Baylor College of Medicine Alumni Association Distinguished Faculty Award in 2004, MDA’s Wings Over Wall Street Diamond Award in 2004, Texas Neurological Society Lifetime Achievement Award in 2005 and the Forbes Norris Award for “compassion and love for humanity in research and treatment in patients with ALS” from the International Alliance of ALS/MND Associations in 2005, and the Museum District Business Alliance Award in recognition of his commitment to research, patient care, and education, 2007, and the recipient of the Houston Academy of Medicine 2008 John P. McGovern Compleat Physician Award. He is also named 2008 Best of the Best Physicians by the Medical Journal Houston.
Research in Dr. Appel’s laboratory has focused on developing new insights into degenerative neurologic diseases with primary emphasis on Amyotrophic Lateral Sclerosis (ALS). More specifically he is studying the importance of immune/inflammatory alterations as well as increased intracellular calcium and free radical stress in ALS, Parkinson’s Disease (PD), and Alzheimer’s Disease. His focus on neuroinflammation stems from his early immunological studies on multiple sclerosis. In PD, his laboratory developed an immune mediated model of nigral neuron injury, and then demonstrated the ability of PD IgG to cause nigral injury in vitro and in vivo. In ALS his laboratory was first to develop an immune-mediated preclinical model of motor neuron disease, and then to document the presence of neuroinflammatory markers including elevated immunoglobulins, activated microglia, and T cell lymphocytes in both the preclinical model and human sporadic ALS. His laboratory has also demonstrated the presence of increased intracellular calcium and altered mitochondria in human sporadic ALS motor neuron axon terminals. This demonstration of increased intracellular calcium was associated with the absence of calcium binding proteins in motor neurons and could help explain the selective vulnerability of motor neurons in ALS. His preclinical studies have also documented enhanced neuroinflammation and activated microglia prior to evidence of clinical disease and motor neuron cell death. Comparable studies in human ALS have employed PCR techniques to confirm the presence of activated microglia, and to demonstrate the presence of immature and mature dendritic cells, and enhanced chemokine signaling. His current studies are focused on defining the intercellular signals between neurons and glia, and between the CNS and the systemic circulation, which could contribute to the pathogenesis of motor neuron injury and cell death. Therapeutic efforts in preclinical models and in human ALS are presently focused on modifying the neuroinflammatory responses with bone marrow stem cell transplantation.
Neuromuscular disorders, Neurodegenerative diseases: Amyotrophic Lateral Sclerosis, Alzheimer’s disease, Parkinson’s disease.
Henkel JS, Beers DR, Wen S, Bowser R, Appel SH. Decreased mRNA expression of tight junction proteins in lumbar spinal cords of ALS patients. Neurology. Submitted Nov. 5, 2008.
Appel SH, Engelhardt JI, Henkel JS, Siklos L, Beers DR, Yen AA, Simpson EP, Luo Y, Carrum G, Heslop HE, Brenner MK, Popat U. Hematopoietic Stem Cell Transplantation in Patients with Sporadic Amyotrophic Lateral Sclerosis. Neurology. 2008 Oct 21;71(17):1326-34.
Beers DR, Henkel JS, Zhao W, Wang J, Appel SH. CD4+T-cells Support Glial Neuroprotection, Slow Disease Progression, and Modify Glial Morphology in an Animal Model of Inherited ALS. Pro Natl Acad Sci USA. 2008, Oct. 7;105(40):15558-63.
Villoslada P, Moreno B, Melero I, Pablos JL, Martino G, Uccelli A, Montalban X, Avila J, Rivest S, Acarin L, Appel S, Khoury SJ, McGeer P, Ferrer I, Delgado M, Obeso J, Schwartz M. Immunotherapy for neurological diseases. Clin Immunol. 2008 Sep;128(3):294-305.
Appel SH, Beers DR, Henkel JS, Zhao W. Novel Therapeutic Targets in Neurodegenerative Diseases: Lessons from Amyotrophic Lateral Sclerosis. Curr Neurol Neurosci Rep. 2008 Sep;8(5):353-5.
Voustianiouk A, Seidel G, Panchal J, Sivak M, Czaplinski A, Yen A, Appel SH, Lange DJ. ALSFRS and Appel ALS scores: discordance with disease progression. Muscle Nerve. 2008 May;37(5):668-72.
Wheaton MW, Salamone AR, Mosnik DM, McDonald RO, Appel SH, Schmolck HI, Ringholz GM, Schulz PE. Cognitive impairment in familial ALS. Neurology. 2007 Oct 2;69(14):1411-7.