Stanley H. Appel, MD

Peggy & Gary Edwards Distinguished Endowed Chair, Stanley H. Appel Department of Neurology
Professor of Neurology, Institute for Academic Medicine
Full Member, Research Institute
Director, Neurological Institute
Houston Methodist
Weill Cornell Medical College

Research Lab


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, Houston 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.

Description of Research

Research in Dr. Appel’s laboratory has focused on developing new insights into neurodegenerative diseases with primary emphasis on ALS. His studies of mutant SOD transgenic mice have documented that neuroinflammation and activated microglia are neuroprotective during early stages of disease and cytotoxic during late stages of disease. The early stages start within motor neurons and appear cell-autonomous, whereas later stages involve innate immune glia and are non-cell autonomous.These two stages appear to be modulated by peripheral Tcells that enter the CNS at sites of neuronal injury; Th2 and regulatory Tcells are increased in early stages and appear to provide neuroprotection, while Th1 Tcells are increased in later stages and mediate cytotoxicity. Transplantation of ALS mice with regulatory Tcells prolonged disease duration by more than 80%. Our comparable studies in human ALS have employed PCR techniques to confirm the presence of activated microglia and to demonstrate the presence of CD4 Tcells as well as immature and mature dendritic cells and enhanced chemokine signaling. Our laboratory was the first to document that regulatory T lymphocytes modulate disease progression in ALS patients. More specifically, regulatory T lymphocytes are decreased in ALS patients that progress at a faster rate; the levels of Treg may thus serve as a biomarker of rates of disease progression. His current efforts are focused on enhancing the protective immunity of Treg cells and anti-inflammatory microglia, and decreasing the proinflammatory immunity of Th1 effector lymphocytes and proinflammatory microglia.

Areas Of Expertise

Neurodegenerative diseases Amyotrophic Lateral Sclerosis Alzheimer’s disease Parkinson’s disease Neuromuscular disorders
Education & Training

, National Heart, Lung, and Blood Institute, National Institutes of Health
, Duke University Medical Center
, Mount Sinai Medical Center
, Harvard University
, Columbia University College of Physicians and Surgeons

A robust, good manufacturing practice-compliant, clinical-scale procedure to generate regulatory T cells from patients with amyotrophic lateral sclerosis for adoptive cell therapy
Alsuliman, A, Appel, SH, Beers, DR, Basar, R, Shaim, H, Kaur, I, Zulovich, J, Yvon, E, Muftuoglu, M, Imahashi, N, Kondo, K, Liu, E, Shpall, EJ & Rezvani, K 2016, Cytotherapy, vol 18, no. 10, pp. 1312-24. DOI:

Stem cells in amyotrophic lateral sclerosis: Ready for prime time?
Appel, SH & Armon, C 2016, Neurology, vol 87, no. 4, pp. 348-349. DOI:

Defining SOD1 ALS natural history to guide therapeutic clinical trial design
Bali, T, Self, W, Liu, J, Siddique, T, Wang, LH, Bird, TD, Ratti, E, Atassi, N, Boylan, KB, Glass, JD, Maragakis, NJ, Caress, JB, McCluskey, LF, Appel, SH, Wymer, JP, Gibson, S, Zinman, L, Mozaffar, T, Callaghan, B, McVey, AL, Jockel-Balsarotti, J, Allred, P, Fisher, ER, Lopate, G, Pestronk, A, Cudkowicz, ME & Miller, TM 2016, Journal of Neurology, Neurosurgery and Psychiatry. DOI:

The immune system continues to knock at the ALS door
Staff, NP & Appel, SH 2016, Neuromuscular Disorders, vol 26, no. 6, pp. 335-336. DOI:

TDP-43 activates microglia through NF-?B and NLRP3 inflammasome
Zhao, W , Beers, DR, Bell, S, Wang, J, Wen, S, Baloh, RH & Appel, SH 2015, Experimental Neurology, vol 273, pp. 24-35. DOI:

Protective and Toxic Neuroinflammation in Amyotrophic Lateral Sclerosis
Hooten, KG, Beers, DR, Zhao, W & Appel, SH 2015, Neurotherapeutics, vol 12, no. 2, pp. 364-375. DOI:

Exome sequencing in amyotrophic lateral sclerosis identifies risk genes and pathways
Cirulli, ET, Lasseigne, BN, Petrovski, S, Sapp, PC, Dion, PA, Leblond, CS, Couthouis, J, Lu, Y-F, Wang, Q, Krueger, BJ, Ren, Z, Keebler, J, Han, Y, Levy, SE, Boone, BE, Wimbish, JR, Waite, LL, Jones, AL, Carulli, JP, Day-Williams, AG, Staropoli, JF, Xin, WW, Chesi, A, Raphael, AR, McKenna-Yasek, D, Cady, J, Vianney de Jong, JMB, Kenna, KP, Smith, BN, Topp, S, Miller, J, Gkazi, A, Al-Chalabi, A, van den Berg, LH, Veldink, J, Silani, V, Ticozzi, N, Shaw, CE, Baloh, RH, Appel, S, Simpson, E, Lagier-Tourenne, C, Pulst, SM, Gibson, S, Trojanowski, JQ, Elman, L, McCluskey, L, Grossman, M, Shneider, NA, Chung, WK, Ravits, JM, Glass, JD, Sims, KB, Van Deerlin, VM, Maniatis, T, Hayes, SD, Ordureau, A, Swarup, S, Landers, J, Baas, F, Allen, AS, Bedlack, RS, Harper, JW, Gitler, AD, Rouleau, GA, Brown, R, Harms, MB, Cooper, GM, Harris, T, Myers, RM, Goldstein, DB & FALS Sequencing Consortium 2015, Science (New York, N.Y.), vol 347, no. 6229, pp. 1436-41. DOI:

Role of Inflammation in Neurodegenerative Diseases
Appel, SH , Beers, DR & Zhao, W 2014, . in Neurobiology of Brain Disorders: Biological Basis of Neurological and Psychiatric Disorders. Elsevier Inc. pp. 380-395. DOI:

Neuroimmunology of Amyotrophic Lateral Sclerosis
Henkel, JS, Beers, DR, Zhao, W & Appel, SH 2014, . in Neuroinflammation and CNS Disorders. Wiley Blackwell, pp. 185-209. DOI:

Appel, SH 2014, Unknown Journal, pp. vii-x. DOI:

TDP-43 pathology in the basal forebrain and hypothalamus of patients with amyotrophic lateral sclerosis
Cykowski, MD, Takei, H, Schulz, PE, Appel, SH & Powell, SZ 2014, Acta Neuropathologica Communications, vol 2, pp. 171. DOI:

Correction to: 'Seeking a measure of clinically meaningful change in ALS'
McElhiney, M, Rabkin, JG, Goetz, R, Katz, J, Miller, RG, Forshew, DA, David, W, Cudkowicz, M, Glass, JD, Appel, S, Simpson, E & Mitsumoto, H 2014, Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, vol 15, no. 7-8. DOI:

An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions
Pattee, GL, Wymer, JP, Lomen-Hoerth, C, Appel, SH, Formella, AE & Pope, LE 2014, Current Medical Research and Opinion, vol 30, no. 11, pp. 2255-2265. DOI:

Seeking a measure of clinically meaningful change in ALS
Mcelhiney, M, Rabkin, JG, Goetz, R, Katz, J, Miller, RG, Forshew, DA, David, W, Cudkowicz, M, Glass, JD, Appel, S, Simpson, E & Mitsumoto, H 2014, Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, vol 15, no. 5-6, pp. 398-405. DOI:

TREM2 variant p.R47H as a risk factor for sporadic amyotrophic lateral sclerosis
Cady, J, Koval, ED, Benitez, BA, Zaidman, C, Jockel-Balsarotti, J, Allred, P, Baloh, RH, Ravits, J, Simpson, E, Appel, SH, Pestronk, A, Goate, AM, Miller, TM, Cruchaga, C & Harms, MB 2014, JAMA Neurology, vol 71, no. 4, pp. 449-453. DOI:

Immune-mediated mechanisms in the pathoprogression of amyotrophic lateral sclerosis
Zhao, W , Beers, DR & Appel, SH 2013, Journal of Neuroimmune Pharmacology, vol 8, no. 4, pp. 888-899. DOI:

Special issue: A tribute to Jenny S. Henkel, Ph.D. (1955-2013).
Appel, SH 2013, Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, vol 8, no. 4, pp. 757-1047.

A Tribute to Jenny S. Henkel, Ph.D. (1955-2013)
Appel, SH 2013, Journal of Neuroimmune Pharmacology, pp. 1-3. DOI:

Deciphering amyotrophic lateral sclerosis: What phenotype, neuropathology and genetics are telling us about pathogenesis
Ravits, J, Appel, S, Baloh, RH, Barohn, R, Rix Brooks, B, Elman, L, Floeter, MK, Henderson, C, Lomen-Hoerth, C, MacKlis, JD, McCluskey, L, Mitsumoto, H, Przedborski, S, Rothstein, J, Trojanowski, JQ, Van Den Berg, LH & Ringel, S 2013, Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, vol 14, no. SUPPL1, pp. 5-18. DOI:

An antisense oligonucleotide against SOD1 delivered intrathecally for patients with SOD1 familial amyotrophic lateral sclerosis: A phase 1, randomised, first-in-man study
Miller, TM, Pestronk, A, David, W, Rothstein, J, Simpson, E, Appel, SH, Andres, PL, Mahoney, K, Allred, P, Alexander, K, Ostrow, LW, Schoenfeld, D, Macklin, EA, Norris, DA, Manousakis, G, Crisp, M, Smith, R, Bennett, CF, Bishop, KM & Cudkowicz, ME 2013, The Lancet Neurology, vol 12, no. 5, pp. 435-442. DOI: