Cure Alzheimer's Fund Cure Alzheimer's Fund

Steven L. Wagner, Ph.D.

University of California, San Diego
(1958–2022)

After obtaining postgraduate degrees in microbiology and molecular genetics, Dr. Steven Wagner started his career studying Alzheimer’s disease at the Salk Institute for Biological Studies. As a member of the team that identified amyloid precursor protein (APP), which has a pivotal role in the pathology of Alzheimer’s disease, he established his importance in the field of research early in his career. An extremely warm individual who made those around him feel special, Dr. Wagner was genuine in his personal goal: to find a cure for Alzheimer’s disease. “When it came to actually translating scientific research into new therapies that might help patients or even end Alzheimer’s disease, once and for all, Steve was second to none,” said his friend and colleague, Dr. Rudy Tanzi. Dr. Tanzi continued, “In 2000, Steve and I co-founded a company to develop a drug that is now one of the field’s greatest hopes for stopping Alzheimer’s disease. When we finally beat Alzheimer’s disease, Steve will have played a major role.”

Related Research:

Comprehensive Analyses of Chronic Efficacy Studies with GSM 776890 for Submission of the Pre-IND Brochure to the FDA Prior to Pre-IND Meeting and IND Filing for the SAD/MAD Phase I Safety/Toxicity and Ultimately for Phase II and Phase III Efficacy Clinical Trials to Support the NDA Steven L. Wagner 2020-08-04 The Effect of Chronic Gamma-Secretase Modulation on the Prevention of Traumatic Brain Injury-Provoked and Alzheimer’s Disease-Relevant Biochemical, Pathological and Behavioral Alterations Steven L. Wagner Brian P. Head 2018-12-24 Biochemical Mapping of the GSM Binding Site of Novel Pyridazine-Derived Small Molecule Gamma-Secretase Modulators Steven L. Wagner Yueming Li 2018-08-09 Binding Site Characterization of a Novel Pyridazine-Derived Class of γ-Secretase Modulators Steven L. Wagner 2016-09-23 Acceleration of FDA-Required GLP Gene Toxicity Studies with the GSM BPN-15606 Steven L. Wagner 2016-04-26 Lead Optimization and Lead Evolution of Potent SGSMs for the Treatment of Alzheimer’s Disease Steven L. Wagner Rudy Tanzi 2015-07-02 Elucidation of the Molecular Target of Potent γ-Secretase Modulators Steven L. Wagner 2014-12-03 Elucidation of the mechanism of action of Gamma Secretase Modulators Steven L. Wagner 2013-07-10 Novel Soluble Gamma-Secretase Modulators for the Treatment of Alzheimer’s Disease Identification of the Molecular Target of Potent Gamma-Secretase Modulators Steven L. Wagner 2011-11-11 Design, Synthesis and Characterization of Novel and Potent Gamma Secretase Modulators: Physiochemical and Pharmacokinetic Properties Steven L. Wagner William C. Mobley 2011-02-12 Novel Soluable Gamma-Secretase Modulators Steven L. Wagner Rudy Tanzi 2011-02-12

Funded Research

These projects were made possible from Cure Alzheimer's Fund support.

Project Description Researchers Funding
Comprehensive Analyses of Chronic Efficacy Studies with GSM 776890 for Submission of the Pre-IND Brochure to the FDA Prior to Pre-IND Meeting and IND Filing for the SAD/MAD Phase I Safety/Toxicity and Ultimately for Phase II and Phase III Efficacy Clinical Trials to Support the NDA 2020

$259,366
The Effect of Chronic Gamma-Secretase Modulation on the Prevention of Traumatic Brain Injury-Provoked and Alzheimer’s Disease-Relevant Biochemical, Pathological and Behavioral Alterations 2018-2019

$460,000
Biochemical Mapping of the GSM Binding Site of Novel Pyridazine-Derived Small Molecule Gamma-Secretase Modulators 2017 and 2019

$600,000
Binding Site Characterization of a Novel Pyridazine-Derived Class of γ-Secretase Modulators 2016

$194,950
Acceleration of FDA-Required GLP Gene Toxicity Studies with the GSM BPN-15606 2016

$144,450
Lead Optimization and Lead Evolution of Potent SGSMs for the Treatment of Alzheimer’s Disease 2015

$476,988
Elucidation of the Molecular Target of Potent γ-Secretase Modulators 2014

$250,000
Elucidation of the mechanism of action of Gamma Secretase Modulators 2013

$150,000
Novel Soluble Gamma-Secretase Modulators for the Treatment of Alzheimer’s Disease Identification of the Molecular Target of Potent Gamma-Secretase Modulators 2011, 2012

$300,000
Design, Synthesis and Characterization of Novel and Potent Gamma Secretase Modulators: Physiochemical and Pharmacokinetic Properties 2009

$200,000
Novel Soluable Gamma-Secretase Modulators 2010

$250,000

Selected Publications

These published papers resulted from Cure Alzheimer’s Fund support.

Kwak, S. S., Washicosky, K. J., Brand, E., von Maydell, D., Aronson, J., Kim, S., Capen, D. E., Cetinbas, M., Sadreyev, R., Ning, S., Bylykbashi, E., Xia, W., Wagner, S. L., Choi, S. H., Tanzi, R. E., & Kim, D. Y. Amyloid-β42/40 ratio drives tau pathology in 3D human neural cell culture models of Alzheimer’s disease, Nature Communications, March 13, 2020, Read More

Caldwell, A. B., Liu, Q., Schroth, G. P., Galasko, D. R., Yuan, S. H., Wagner, S. L., & Subramaniam, S. Dedifferentiation and neuronal repression define familial Alzheimer’s disease., Science Advances, November 13, 2020, Read More

Wagner, S. L., Zhang, C., Cheng, S., Nguyen, P., Zhang, X., Rynearson, K. D., Wang, R., Li, Y., Sisodia, S. S., Mobley, W. C., & Tanzi, R. E. Soluble gamma-secretase modulators slectively inhibit the production of the 42 amino-acid amyloid beta peptide variant and augment the production of multiple carboxy-truncated amyloid beta species, Biochemistry, January 22, 2014, Read More

Zhang, X., Hoey, R., Koide, A., Dolios, G., Paduch, M., Nguyen, P., Wu, X., Li, Y., Wagner, S. L., Wang, R., Koide, S., & Sisodia, S. S. A synthetic antibody fragment targeting nicastrin affects assembly and trafficking of gamma-secretase, Journal of Biological Chemistry, October 28, 2014, Read More

Andrew, R. J., Fernandez, C. G., Stanley, M., Jiang, H., Nguyen, P., Rice, R. C., Buggia-Prévot, V., De Rossi, P., Vetrivel, K. S., Lamb, R., Argemi, A., Allaert, E. S., Rathbun, E. M., Krause, S. V., Wagner, S. L., Parent, A. T., Holtzman, D. M., & Thinakaran, G. Lack of BACE1 S-palmitoylation reduces amyloid burden and mitigates memory deficits in transgenic mouse models of Alzhiemer’s disease, Proceedings of the National Academy of Sciences of the United States of America, October 23, 2017, Read More

Barros, M., Houlihan, W. J., Paresi, C. J., Brendel, M., Rynearson, K. D., Lee, C. W., Prikhodko, O., Cregger, C., Chang, G., Wagner, S. L., Gilchrist, M. L., & Li, Y. M. Gamma-Secretase Partitioning Into Lipid Bilayers Remodels Membrane Microdomains After Direct Insertion, Langmuir, May 20, 2020, Read More

Rynearson, K. D., Ponnusamy, M., Prikhodko, O., … Mobley, W. C., Thinakaran, G., Tanzi, R. E., Wagner, S. L. Preclinical validation of a potent γ-secretase modulator for Alzheimer’s disease prevention, Journal of Experimental Medicine, March 2, 2021, Read More

Xu, Y., Wang, C., Wey, H. Y., Liang, Y., Chen, Z., Choi, S. H., Ran, C., Rynearson, K. D., Bernales, D. R., Koegel, R. E., Fiedler, S. A., Striar, R., Wagner, S. L., Tanzi, R. E., & Zhang, C. Molecular imaging of Alzheimer’s disease–related gamma-secretase in mice and nonhuman primates, Journal of Experimental Medicine, December 7, 2020, Read More

D'Avanzo, C., Sliwinski, C., Wagner, S. L., Tanzi, R. E., Kim, D. Y., & Kovacs, D. M. Gamma-Secretase modulators reduce endogenous amyloid beta (42) levels in human neural progenitor cells without altering neuronal differentiation, The FASEB Journal, April 22, 2015, Read More

Wagner, S. L., Rynearson, K. D., Duddy, S. K., Zhang, C., Nguyen, P. D., Becker, A., Vo, U., Masliah, D., Monte, L., Klee, J. B., Echmalian, C. M., Xia, W., Quinti, L., Johnson, G., Lin, J. H., Kim, D. Y., Mobley, W. C., Rissman, R. A., & Tanzi, R. E. Pharmacological and Toxicological Properties of the Potent Oral gamma-secretase modulator BPN-15606, Journal of Pharmacology and Experimental Therapeutics, July 1, 2017, Read More

Caldwell, A. B., Anantharaman, B. G., Ramachandran, S., Nguyen, P., Liu, Q., Trinh, I., Galasko, D. R., Desplats, P. A., Wagner, S. L., & Subramaniam, S. Transcriptomic profiling of sporadic Alzheimer’s disease patients, Molecular Brain, October 12, 2022, Read More

Liu, Q., Waltz, S., Woodruff, G., Ouyang, J., Israel, M. A., Herrera, C., Sarsoza, F., Tanzi, R. E., Koo, E. H., Ringman, J. M., Goldstein, L. S., Wagner, S. L., & Yuan, S. H. Effect of potent gamma-secretase modulator in human neurons derived from multiple presenilin 1-induced pluripotent stem cell mutant carriers., JAMA Neurology, December 1, 2014, Read More

Choi, S. H., Kim, Y. H., Hebisch, M., Sliwinski, C., Lee, S., D'Avanzo, C., Chen, H., Hooli, B., Asselin, C., Muffat, J., Klee, J. B., Zhang, C., Wainger, B. J., Peitz, M., Kovacs, D. M., Woolf, C. J., Wagner, S. L., Tanzi, R. E., & Kim, D. Y. A Three-dimensional human neural cell culture model of Alzheimer’s disease, Nature, October 12, 2014, Read More

Weissmiller, A. M., Natera-Naranjo, O., Reyna, S. M., Pearn, M. L., Zhao, X., Nguyen, P., Cheng, S., Goldstein, L. S., Tanzi, R. E., Wagner, S. L., Mobley, W. C., & Wu, C. A gamma secretase inhibitor, but not a gamma-secretase modulator, induced defects in BDNF Axonal trafficking and signaling: evidence for a role for APP, PLoS One, February 24, 2015, Read More

Raven, F., Ward, J. F., Zoltowska, K. M., Wan, Y., Bylykbashi, E., Miller, S. J., Shen, X., Choi, S. H., Rynearson, K. D., Berezovska, O., Wagner, S. L., Tanzi, R. E., & Zhang, C. Soluble Gamma-secretase Modulators Attenuate Alzheimer’s beta amyloid pathology and induce conformational changes in presenili 1, eBioMedicine, September 4, 2017, Read More

Prikhodko, O., Rynearson, K. D., Sekhon, T., Mante, M. M., Nguyen, P. D., Rissman, R. A., Tanzi, R. E., & Wagner, S. L. The GSM BPN-15606 as a Potential Candidate for Preventative Therapy in Alzheimer’s Disease, Journal of Alzheimer's Disease, February 18, 2020, Read More

Caldwell, A. B., Liu, Q., Zhang, C., Schroth, G. P., Galasko, D. R., Rynearson, K. D., Tanzi, R. E., Yuan, S. H., Wagner, S. L., & Subramaniam, S. Endotype reversal as a novel strategy for screening drugs targeting familial Alzheimer’s disease, Alzheimer's & Dementia, January 27, 2022, Read More

Kim, M., Suh, J., Romano, D., Truong, M. H., Mullin, K., Hooli, B., Norton, D., Tesco, G., Elliott, K., Wagner, S. L., Moir, R. D., Becker, K. D., & Tanzi, R. E. Potential late-onset Alzheimer’s disease-associated mutations in the ADAM10 gene attenuate alpha-secretase activity, Human Molecular Genetics, October 15, 2009, Read More

Rynearson, K. D., Buckle, R. N., Herr, R. J., Mayhew, N. J., Chen, X., Paquette, W. D., Sakwa, S. A., Yang, J., Barnes, K. D., Nguyen, P., Mobley, W. C., Johnson, G., Lin, J. H., Tanzi, R. E., & Wagner, S. L. Design and synthesis of novel methoxypyridine-derived gamma-secretase modulators, Bioorganic and Medicinal Chemistry, September 1, 2020, Read More

Deyts, C., Clutter, M., Pierce, N., Chakrabarty, P., Ladd, T. B., Goddi, A., Rosario, A. M., Cruz, P., Vetrivel, K., Wagner, S. L., Thinakaran, G., Golde, T. E., & Parent, A. T. APP-Mediated signaling prevents memory decline in Alzheimer’s disease mouse model, Cell Reports, April 30, 2019, Read More

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