Select publications about our development pipeline of innovative therapeutics

These articles or posters contain information about investigational compounds that are not approved by the FDA. The safety and efficacy of these products have not been established.

 

Human Clinical Studies. Phase 2a publications

 

Bakker, A., Krauss, G.L., Albert, M.S., Speck, C.L., Jones, L.R., Stark, C.E., Yassa, M.A., Bassett, S.S., Shelton, A.L., & Gallagher, M. (2012). Reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment. Neuron, 74(3): 467-474. PMID: 22578498; PMCID: PMC3351697.

 

Bakker, A., Albert, M. S., Krauss, G., Speck, C. L., Gallagher, M. (2015).   Response of the medial temporal lobe network in amnestic mild cognitive impairment to therapeutic intervention assessed by fMRI and memory task performance. NeuroImage: Clinical. 2015 Feb 21;7:688-98. doi: 10.1016/j.nicl.2015.02.009. [eCollection 2015]. PMID: 25844322; PMCID: PMC4377841.

 

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Human Clinical Studies: Publications Relevant to Phase 2/3 Program

 

Tran, T., Speck, C., Pisupati, A., Gallagher, M., Bakker, A. (2016) Increased hippocampal activation in ApoE-4 carriers and non-carriers with amnestic mild cognitive impairment. NeuroImage: Clinical. 13:237-245. PMID: 28070483

 

Tward, D. J., Sicat, C. S., Brown, T., Bakker, A., Gallagher, M., Albert, M., Miller, M., Alzheimer’s Disease Neuroimaging Initiative. (2017). Entorhinal and transentorhinal atrophy in mild cognitive impairment using longitudinal diffeomorphometry. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 9, 41-50. PMID: 28971142; PMCID: PMC5608074

 

Kulason, S., Tward, D. J., Brown, T., Sicat, C. S., Liu, C. F., Ratnanather, J. T., Younes, L., Bakker A, Gallagher M, Albert A, Miller, MI & Alzheimer’s Disease Neuroimaging Initiative. (2019). Cortical thickness atrophy in the transentorhinal cortex in mild cognitive impairment. NeuroImage: Clinical, 21, 101617. PMID: 30552075; PMCID: PMC6412863

 

Kulason, S., Xu, E., Tward, D. J., Bakker, A., Albert, M., Younes, L., & Miller, M. I. (2020). Entorhinal and transentorhinal atrophy in preclinical Alzheimer’s disease. Frontiers in Neuroscience, 14. PMID: 32973425; PMCID: PMC7472871

 

Corona‐Long, C. A., Tran, T. T., Chang, E., Speck, C. L., Gallagher, M., & Bakker, A. (2020). Comparison of male and female patients with amnestic mild cognitive impairment: Hippocampal hyperactivity and pattern separation memory performance. Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring, 12(1), e12043.

 

Rosenzweig‐Lipson, S., Barton, R., Gallagher, M., Edgar, C. J., Maruff, P. T., & Mohs, R. (2020). HOPE4MCI trial: First trial targeting reduction of hippocampal overactivity to treat mild cognitive impairment due to Alzheimer’s disease with AGB101: Human/Human trials: Other. Alzheimer’s & Dementia, 16, e045331.

 

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Human Clinical Studies: Consistent with AgeneBio’s Approach

 

Dickerson, B.C., Salat, D.H., Greve, D.N., Chua, E.F., Rand-Giovannetti, E., Rentz. D.M., Bertram, L., Mullin, K., Tanzi, R.E., Blacker, D., & Albert, M.S. (2005) Increased hippocampal activation in mild cognitive impairment compared to normal aging and AD. Neurology, 65(3): 404-411.

 

Yassa, M.A,. Stark, S.M., Bakker, A., Albert, M.S., Gallagher, M., Stark, & C.E. (2010) High-resolution structural and functional MRI of hippocampal CA3 and dentate gyrus in patients with amnestic Mild Cognitive Impairment. Neuroimage 51: 1242-1252. 

 

Putcha, D., Brickhouse, M., O’Keefe, K., Sullivan, C., Rentz, D., Marshall, G., Dickerson, B., & Sperling, R. (2011) Hippocampal hyperactivation associated with cortical thinning in Alzheimer’s disease signature regions in non-demented elderly adults. The Journal of Neuroscience 31: 17680-17688. 

 

Huijbers, W., Mormino, E.C., Schultz, A.P., Wigman, S., Ward, A.M., Larvie, M., Amariglio, R.E., Marshall, G.A., Rentz, D.M., Johnson, K.A., & Sperling, R.A. (2015) Amyloid-β deposition in mild cognitive impairment is associated with increased hippocampal activity, atrophy and clinical progression. Brain 138: 1023-1035.

 

Leal, S.L., Landau, S.M., Bell, R.K., & Jagust, W.J. (2017) Hippocampal activation is associated with longitudinal amyloid accumulation and cognitive decline. Elife 6: e22978.

 

Marks, S.M., Lockhart, S.N., Baker, S.L., & Jagust, W.J. (2017) Tau and β-amyloid are associated with medial temporal lobe structure, function and memory encoding in normal aging. The Journal of Neuroscience: 3769-16.

 

Huijbers, W., Schultz, A.P., Papp, K.V., LaPoint, M.R., Hanseeuw, B., Chhatwal, J., Hedden, T., Johnson, K.A. & Sperling, R.  (2019) Tau accumulation in clinically normal older adults is associated with hippocampal hyperactivity. The Journal of Neuroscience. 39: 548-556.

 

Berron, D., Cardenas-Blanco, A., Bittner, D., Metzger, C.D., Spottke, A., Heneka, M.T., Liessbach, K., Schneider, A., Teipel, S.J., Wagner, M., Speck, O., Jenssen, F., & Duzel, E. (2019) Higher CSF Tau levels are related to hippocampal hyperactivity and object mnemonic discrimination in older adults. (2019) The Journal of Neuroscience. 39: 8788-8797.

 

Richter, N., Bischof, G., Dronse, J., Nellessen, N., Neumaier, B., Langen, K.-J., Drzezga, A., Fink, G.R., van Eimeren, T., Kukolja, J., & Onur, O.A.   Entorhinal tau predicts hippocampal activation and memory deficits in Alzheimer’s disease. (2020) Journal of Alzheimer’s Disease. 78: 1601-1604.

 

Mattson-Carlgren, N., Janelidze, S., Palmqvist, S., Cullen, N., Svenningsson, A.L., Strandberg, O., Mengel, D., Walsh, D.M., Stomrud, E., Dage, J.L., Hansson, O. (2020) Brain. 143: 3234-3241.

 

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Preclinical Studies Supportive of targeting Hyperactivity*(includes levetiracetam data)

 

*Koh, M.T., Haberman, .RP., Foti, S., McCown, T.J., Gallagher, M. (2010) Treatment strategies targeting excess hippocampal activity benefit aged rats with cognitive impairment. Neuropsychopharmacology 35: 1016-1025. 

 

Busche, M.A., Chen, X., Henning, H.A., Reichwald, J., Staufenbield, M., Sakmann, B., Konnerth, A. (2012) Critical role of soluble amyloid-β for early hippocampal hyperactivity in a mouse model of Alzheimer’s disease. Proceedings of the National Academy of Sciences USA 109: 8740-8745. 

 

*Sanchez, P.E., Zhu, L., Verret, L., Vosse,l K.A., Orr, A.G., Cirrito, J.R., Devidze, N., Ho, K., Yu, G.Q., Palop, J.J., Mucke, L. (2012) Levetiracetam suppresses neuronal network dysfunction and reverses synaptic and cognitive deficits in an Alzheimer’s disease model. Proceedings of the National Academy of Sciences USA 109: E2 895–E2 903. 

 

*Suberbielle, E., Sanchez, P.E., Kravitz, A.V., Wang, X., Ho, K., Eilertson, K., Devidze, N., Kreitzer, A.C., Mucke, L. (2013) Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β. Nature Neuroscience 16: 613-621. 

 

Koh, M.T., Rosenzweig-Lipson, S., & Gallagher, M. (2013). Selective GABAA ∝5 positive allosteric modulators improve cognitive function in aged rats with memory impairment. Neuropharmacology, 64: 145-152. PMID: 22732440; PMCID: PMC3445657.

 

*Shi J-Q, Wang B-R, Tian Y-Y, Xu J, Gao L, Zhao S-L, Jiang T, Xie H-G, Zhang Y-D (2013) Antiepileptics topiramate and levetiracetam  alleviate behavioral deficits and reduce neuropathology in APPswe/PS1dE9 transgenic mice.  CNS Neuroscience and Therapeutics 1-11.

 

*Hall, A.M., Throesch, B.T., Buckingham, S.C., Markwardt, S.J., Peng, Y., Wang, Q., Hoffman, D.A., Roberson, E.D. (2015) Tau-dependent Kv4.2 depletion and dendritic hyperexcitablilty in a mouse model of Alzheimer’s Disease.  The Journal of Neuroscience 35(15):6221-6230.

 

*Sendrowski, K., Sobainiec, W., Stasiak-Barmuta, A., Sobaniec, P., Popko, J. (2015) Study of the protective effects of a nootropic agents against neuronal damage induced by amyloid-beta (fragment 25-35) in cultured hippocampal neurons. Pharmacological Reports 67: 326-331.

 

*Tabuchi, M., Lone, S.R., Liu, S., Liu, Q., Zhang, J., Spira, A.P., & Wu, M.N. (2015) Sleep interacts with Aβ to modulate intrinsic neuronal excitability.  Current Biology 25: 702-712.

 

*Stockburger, C., Miano, D., Baeumlisberger, M, et al. A mitochondrial role of SV2a protein in aging and Alzheimer’s disease: studies with levetiracetam. (2016) J Alzheimers Dis 50:201-215.

 

Yuan, P. & Grutzendler, J. (2016) Attenuation of β-amyloid deposition and neurotoxicity by chemogenetic modulation of neural activity. Journal of Neuroscience 36(2): 632-641.

 

Wu, J.W., Hussaini, S.A., Bastille, M., Rodriguez, G.A., Mrejeru, A., Rilett, K., Sanders, D.W., Cook, C., Fu, H., Boonen, R.A., Herman, M. (2016) Neuronal activity enhances tau propagation and tau pathology in vivo. Nature neuroscience 19(8): 1085.

 

Maeda, S., Djukic, B., Taneja, P., Yu, G.Q., Lo, I., Davis, A., Craft, R., Guo, W., Wang, X., Kim, D., & Ponnusamy, R. (2016) Expression of A152T human tau causes age‐dependent neuronal dysfunction and loss in transgenic mice. EMBO Reports, 17(4): 530-551.

 

Haberman, R., Koh, M.T., Gallagher, M. (2017) Heightened cortical excitability in aged rodents with memory impairment. Neurobiology of Aging. 54:144-151. PMID: 28104309; PMCID: PMC5401793

 

*Das, M., Maeda, S., Hu, B., Yu, G.Q., Guo, W., Lopez, I., Yu, X., Tai, C., Wang, X., Mucke, L. (2018) Neuronal levels and sequence of tau modulate the power of brain rhythms. Neurobiology of Disease 117:181-188.

 

Gallagher, M., Okonkwo, O., Resnick, S., Jagust, W., Benzinger, T., Rapp, P. (2019). What are the threats to successful brain and cognitive aging? Neurobiology of Aging, 83: 130-134. PMID: 31732016; PMCID: PMC6859944

 

Koh, M.T., Branch, A., Haberman, R., & Gallagher, M. (2020). Significance of inhibitory recruitment in aging with preserved cognition: limiting gamma-aminobutyric acid type A α5 function produces memory impairment. Neurobiology of Aging, 91, 1-4.

 

*Rao, N.R. & Save, J.N. (2021) Levetiracetam treatment normalizes levels of the endocytosis machinery and restores non-amyloidogenic APP processing in APP knock-in mice. bioRxiv preprint doi: https://doi.org/10.1101/2021.02.22.432282; this version posted February 22, 2021.