Gary Armstrong, PhD
Gary Armstrong is an Associate Professor and Killam Research Scholar in the Department of Neurology and Neurosurgery at the Montreal Neurological Institute and Hospital. His research focuses on furthering our understanding of the disease process arising in the neurodegenerative disorder Amyotrophic Lateral Sclerosis (ALS).鈥疶o investigate this disease, his research team uses zebrafish as this experimental model can be used to investigate defects that arise in synaptic function using electrophysiological, optogenetic, and imaging approaches. In addition, zebrafish are powerful genetic models that lend easily to genomic manipulations where analogous disease-associated mutations (found in patients that come to the ALS clinic) can be edited into zebrafish orthologs of human genes involved with ALS (e.g. TARDBP, FUS, CHCHD10, TBK1, DNAJC7 and SPTLC1) using the clustered regularly interspaced short palindromic repeats (CRISPRs) mutagenic system. These novel gene-edited animal models permit investigations of disease-causing variants in a native context e.g., whereby similar expression levels and patterns are preserved as opposed to transgenic over-expression animal models that often rely upon non-endogenous promotors to confer a disease phenotypes. 听
In addition to the fundamental research, the Armstrong laboratory is also involved in translational therapeutic drug discovery and the development of gene therapies using antisense oligonucleotides (ASOs). To this end, his research team has developed a zebrafish drug screening platform that bridges research made by scientists working with cellular models of neurodegenerative diseases with zebrafish models thereby providing in vivo readouts of therapeutic recovery of motor and synaptic function. 听
Armstrong obtained his M.Sc. (2003-2005) and PhD鈥�(2005-2009) at Queen鈥檚 University, Kingston Ontario, where he studied adaptations that confer neuroprotection of circuit function during acute exposures to stress (hyperthermia/hypothermia and hypoxia/anoxia). His Postdoctoral research was carried out in the Department of Pathology and Cell Biology (2010-2014) at Universit茅 de Montr茅al and later in the Department of Neurosciences (2014-2016) at the CRCHUM in Montreal, Qu茅bec, where he conducted research examining synaptic defects in ALS zebrafish models.听
Petel L茅gar茅, V., Harji, Z.A., Rampal, C.J. Antonicka, H., Gurberg, T.J.N., Persia, O., E.C. Rodr铆guez听 Shoubridge, E.A., G.A.B. Armstrong. CHCHD10 P80L knock-in zebrafish display a mild ALS-like Phenotype. Experimental Neurology. 382: 114945 (2024).听
Petel L茅gar茅, V., Rampal, C.J. Gurberg, T.J.N., Aaltonen, M.J., Janer, A., Zinman, L., Shoubridge, E.A., G.A.B. Armstrong. Loss of mitochondrial Chchd10 or Chchd2 in zebrafish leads to an ALS-like phenotype and Complex I deficiency independent of the mitochondrial integrated stress response. Developmental Neurobiology. 84:54-69 (2023).听
V. Petel L茅gar茅, C.J. Rampal, T.J.N. Gurberg, Z.A. Harji, X. Allard-Chamard, E.C. Rodr铆guez, G.A.B. Armstrong. Development of an endogenously myc-tagged TARDBP (TDP-43) zebrafish model using the CRISPR/Cas9 system and homology directed repair. Comparative Biochemistry and Physiology Part B. 261, 110756 (2022).听
R. Kumar, V. Francis, G. Kulasekaran, M. Khan, G.A.B. Armstrong, McPherson P.S. A cell-based GEF assay reveals new substrates for DENN domains and a role for DENND2B in primary ciliogenesis. Science Advances. 8, eabk3088: 1-17 (2022).听听
L. Sacconi, L. Silvestri, E.C. Rodr铆guez*, G.A.B. Armstrong, F.S. Pavone, A. Shrier, G. Bub. KHz-rate volumetric voltage imaging of the whole zebrafish heart. Biophysical Reports 2(1): 1-7 (2022).听听
Goldshtein, H., Muhire, A., Petel L茅gar茅, V., Pushett, A., Rotkopf, R., Shefner, J.M. Peterson, RT., Armstrong, G.A,B., Russek- Blum, N.听 Efficacy of Ciprofloxacin/Celecoxib in models of amyotrophic lateral sclerosis. Submitted to Annals of Clinical and Translational Neurology. 7(10): 1883鈥�1897 (2020).听
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This project led to a phase 2a clinical trial titled: 鈥淥pen Label Study to Evaluate the Safety, Tolerability and Preliminary Efficacy of Ciprofloxacin/Celecoxib Combination in Patients With ALS鈥�. ClinicalTrials.gov Identifier: NCT04165850听
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This project has now led to a second phase 2b trial 鈥淎 Multiple-Dose PK Study to Evaluate the Comparative Bioavailability of PrimeC Tablets to Ciprofloxacin Tablets Co-administered With Celecoxib Capsules, in Healthy Adult Subject. ClinicalTrials.gov Identifier: NCT05436678听
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This project will now move onto a Phase III trial coordinated between NeuroSense Therapeutics and Biogen.听
Bose, P., Tremblay, E., Maois, C., Narasimhan, V., Liao, M., Armstrong, G.A.B., Parker, J.A., Robitaille, R., Wen, X.Y., Barden, C. and P. Drapeau. The novel small molecule TRVA242 stabilizes neuromuscular junction defects in multiple animal models of Amyotrophic Lateral Sclerosis. Neurotherapeutics. Pages 1-18 (2019).听
Petel-L茅gar茅, V.*, Harji, Z.A.*, Rampal, C.J., Allard-Chamard, E., Rodriguez, E.C., and Armstrong, G.A.B. Augmentation of spinal cord glutamatergic synaptic currents in zebrafish primary motoneurons expressing mutant human TARDBP (TDP-43). Scientific Reports. 9(1):9122 (2019). *Co-first author.听
Bose, P., Armstrong, G.A.B., and P. Drapeau. Neuromuscular junction abnormalities in a zebrafish听听听听 loss-of-function model of TDP-43. Journal of Neurophysiology. 121(1): 285-297 (2019).听
Armstrong, G.A.B., L贸pez-Guerrero, J.J., Dawson-Scully, K.D., Pe帽a, F., and Robertson, R.M. Inhibition of protein kinase G activity protects neonatal mouse respiratory network from hyperthermic and hypoxic stress. Brain Research. 1311:64-72 (2010).
Armstrong G.A.B., Rodgers C.I., Money T.G.A., and Robertson R.M. Suppression of spreading depression-like events in locusts by inhibition of the NO/cGMP/PKG pathway. The Journal of Neuroscience. 29:8225-8235 (2009).
Armstrong, G.A.B., Shoemaker, K.L., Money, T.G.A., and Robertson, R.M. Octopamine mediates thermal preconditioning of the locust ventilatory CPG via a cAMP/PKA signaling pathway. The Journal of Neuroscience. 26: 12118-12126 (2006).
