Stanley H. Appel, MD

Peggy & Gary Edwards Distinguished Chair in ALS Research, Stanley H. Appel Department of Neurology
Professor of Neurology, Academic Institute
Full Member, Research Institute
Director, Ann Kimball & John W. Johnson Center for Cellular Therapeutics
Houston Methodist
Weill Cornell Medical College

Peggy and Gary Edwards ALS Lab


Dr. Appel is former chair of the Stanley H. Appel Department of Neurology, Professor of Neurology at Weill Cornell Medical College, and the Peggy and Gary Edwards Distinguished Chair for the Treatment and Research of ALS at the Houston Methodist Research Institute. 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/ALSA ALS Research and Clinical Center at Houston 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 focuses on developing new insights into neurodegenerative diseases, with a primary emphasis on amyotrophic lateral sclerosis (ALS).  The major goal is to develop therapeutics that suppress neuroinflammation and the immune/inflammatory alterations that drive neurodegenerative disease progression. In the mSOD1 mouse model of ALS, activated microglia, and T-cell lymphocytes drive disease progression. In vitro studies documented that motor neuron cytotoxicity is produced by pro-inflammatory M1 microglia, and neuroprotection is mediated by anti-inflammatory M2 microglia. The motor neuron injury that initiates the process can be reproduced in vitro with misfolded proteins (mSOD, TDP-43, and FUS) which activate microglia and promote an M1 phenotype that kills motor neurons. Neuroprotective cytokines IL-4 and IL10 released from M2 microglia/macrophages enhance motor neuron survival. In vitro Tregs not only suppress proliferation of Th1, but also suppress pro-inflammatory M1 microglia. These studies suggest that during early stages of disease, motor neurons are capable of intracellular repair abetted by surrounding glia enhanced and modulated by Tregs. However, with increasing injury within the motor neuron, misfolded proteins or their surrogates are released as danger signals and promote the pro-inflammatory M1 phenotype, diminishing protective Tregs and enhancing pro-inflammatory Th1 and Th17.

Areas Of Expertise

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

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

A phase 1 proof-of-concept study evaluating safety, tolerability, and biological marker responses with combination therapy of CTLA4-Ig and interleukin-2 in amyotrophic lateral sclerosis
Thonhoff, JR, Beers, DR, Zhao, W, Faridar, A, Thome, A, Wen, S, Zhang, A, Wang, J & Appel, SH 2024, , Frontiers in Neurology, vol. 15, 1415106.

A phase 1 open-label pilot study of low-dose interleukine-2 immunotherapy in patients with Alzheimer’s disease
Faridar, A, Eid, AM, Thome, AD, Zhao, W, Beers, DR, Pascual, MB, Nakawah, MO, Roman, GC, Davis, CS, Grundman, M, Masdeu, JC & Appel, SH 2023, , Translational Neurodegeneration, vol. 12, no. 1, 54, pp. 54.

A phase 1 open-label pilot study of low-dose interleukine-2 immunotherapy in patients with Alzheimer's disease
Faridar, A, Eid, AM, Thome, AD, Zhao, W, Beers, DR, Pascual, MB, Nakawah, MO, Roman, GC, Davis, CS, Grundman, M, Masdeu, JC & Appel, SH 2023, , Translational Neurodegeneration, vol. 12, no. 1, pp. 54.

Design and Statistical Innovations in a Platform Trial for Amyotrophic Lateral Sclerosis
for the Healey ALS Platform Trial Study Group 2023, , Annals of Neurology.

Primary visual cortex pathology in ALS patients with C9ORF72 expansion
Cykowski, MD, Arumanayagam, AS, Powell, SZ & Appel, SH 2023, , Brain Pathology.

Neuroinflammation co-localizes highly with tau in amnestic mild cognitive impairment
Appleton, J, Funk, Q, Bradbury, K, Yu, M, Faridar, A, Beers, D, Appel, SH, Fujita, M, Masdeu, JC & Pascual, B 2022, , Alzheimers and Dementia, vol. 18, no. S1, e068025.

Combined Regulatory T-Lymphocyte and IL-2 Treatment Is Safe, Tolerable, and Biologically Active for 1 Year in Persons With Amyotrophic Lateral Sclerosis
Thonhoff, JR, Berry, JD, Macklin, EA, Beers, DR, Mendoza, PA, Zhao, W, Thome, AD, Triolo, F, Moon, JJ, Paganoni, S, Cudkowicz, M & Appel, SH 2022, , Neurology: Neuroimmunology and NeuroInflammation, vol. 9, no. 6, e200019.

Ex vivo expanded human regulatory T cells modify neuroinflammation in a preclinical model of Alzheimer’s disease
Faridar, A, Vasquez, M, Thome, AD, Yin, Z, Xuan, H, Wang, JH, Wen, S, Li, X, Thonhoff, JR, Zhao, W, Zhao, H, Beers, DR, Wong, STC, Masdeu, JC & Appel, SH 2022, , Acta Neuropathologica Communications, vol. 10, no. 1, 144.

Extracellular Vesicles Derived From Ex Vivo Expanded Regulatory T Cells Modulate In Vitro and In Vivo Inflammation
Thome, AD, Thonhoff, JR, Zhao, W, Faridar, A, Wang, J, Beers, DR & Appel, SH 2022, , Frontiers in immunology, vol. 13, 875825, pp. 875825.

Adaptive Platform Trials to Transform Amyotrophic Lateral Sclerosis Therapy Development
for the Healey ALS Platform Trial Study Group, HEALEY ALS Platform Trial Study Group, Biostatisticians, Investigators, Clinical Operations Team & Medical Monitors 2022, , Annals of Neurology, vol. 91, no. 2, pp. 165-175.

Tregs Attenuate Peripheral Oxidative Stress and Acute Phase Proteins in ALS
Beers, DR, Thonhoff, JR, Faridar, A, Thome, AD, Zhao, W, Wen, S & Appel, SH 2022, , Annals of Neurology, vol. 92, no. 2, pp. 195-200.

Modulation of spontaneous motor unit potentials by a new motor cortical magnetic stimulation method in amyotrophic lateral sclerosis
Helekar, SA, Thonhoff, J, John, BS, Nguyen, L, Rosenfield, DB & Appel, SH 2022, , Journal of Neurology, vol. 269, no. 10, pp. 5487-5496.

The role of inflammation in neurodegenerative diseases
Appel, SH, Beers, DR & Zhao, W 2022, . in Neurobiology of Brain Disorders: Biological Basis of Neurological and Psychiatric Disorders, Second Edition. Elsevier, pp. 403-421.

Amyotrophic lateral sclerosis is a systemic disease: peripheral contributions to inflammation-mediated neurodegeneration
Appel, SH, Beers, DR & Zhao, W 2021, , Current opinion in neurology, vol. 34, no. 5, pp. 765-772.

Beneficial effects of transplanted human bone marrow endothelial progenitors on functional and cellular components of blood-spinal cord barrier in ALSMice
Garbuzova-Davis, S, Boccio, KJ, Llauget, A, Shell, R, Hailu, S, Mustafa, H, Ehrhart, J, Sanberg, PR, Appel, SH & Borlongan, CV 2021, , eNeuro, vol. 8, no. 5, ENEURO.0314-21.2021.

Fast progression in amyotrophic lateral sclerosis is associated with greater tdp-43 burden in spinal cord
Cathcart, SJ, Appel, SH, Peterson, LE, Greene, EP, Powell, SZ, Arumanayagam, AS, Rivera, AL & Cykowski, MD 2021, , Journal of Neuropathology and Experimental Neurology, vol. 80, no. 8, pp. 754-763.

Radicava/Edaravone Findings in Biomarkers From Amyotrophic Lateral Sclerosis (REFINE-ALS): Protocol and Study Design
Berry, J, Brooks, B, Genge, A, Heiman-Patterson, T, Appel, S, Benatar, M, Bowser, R, Cudkowicz, M, Gooch, C, Shefner, J, Westra, J, Agnese, W, Merrill, C, Nelson, S & Apple, S 2021, , Neurology: Clinical Practice, vol. 11, no. 4, pp. E472-E479.

Ex vivo expansion of dysfunctional regulatory T lymphocytes restores suppressive function in Parkinson’s disease
Thome, AD, Atassi, F, Wang, J, Faridar, A, Zhao, W, Thonhoff, JR, Beers, DR, Lai, EC & Appel, SH 2021, , npj Parkinsons Disease, vol. 7, no. 1, 41, pp. 41.

Detection of endothelial cell-associated human DNA reveals transplanted human bone marrow stem cell engraftment into CNS capillaries of ALS mice
Garbuzova-Davis, S, Boccio, KJ, Ehrhart, J, Sanberg, PR, Appel, SH & Borlongan, CV 2021, , Brain Research Bulletin, vol. 170, pp. 22-28.

Neuroinflammation is highest in areas of disease progression in semantic dementia
Pascual, B, Funk, Q, Zanotti Fregonara, P, Cykowski, MD, Veronese, M, Rockers, E, Bradbury, K, Yu, M, Nakawah, MO, Román, GC, Schulz, PE, Arumanayagam, AS, Beers, D, Faridar, A, Fujita, M, Appel, SH & Masdeu, JC 2021, , Brain, vol. 144, no. 5, pp. 1565-1575.