Research & Development

Discovery Programs

Alzheimer Tau

Alzheimer Tau

AXON Neuroscience has more than 500 cumulative years of experience in neuroimmunology research. AXON Neuroscience has developed a novel approach using monoclonal antibodies as structural imprints of diseased forms of tau proteins isolated from Alzheimer's disease brains. These imprints have been used to identify a novel target for AD therapy – Alzheimer tau.

AXON Immunotherapy program

AXON Alzheimer‘s disease immunotherapy program (ADIP)

AXON Neuroscience is developing new immunotherapeutics targeting Alzheimer tau that can prevent the formation of tau oligomers and neurofibrillary tangles and thus protect the brain from neurodegeneration. These therapeutic approaches have been tested in preclinical studies in AXON animal models. AXON Neuroscience developed active and passive vaccines that eliminate Alzheimer tau by targeting its most vulnerable part.

Axon AD rat model

AXON Alzheimer's disease diagnostic program (ADDP)

AXON Neuroscience discovered a novel pathological form of tau protein critical for development of AD and present only in AD patients. Based on this knowledge, AXON Neuroscience is developing new diagnostic tools for early and late stages of AD.

Axon AD rat model

AXON Alzheimer's disease preclinical platforms (ADPP)

AXON Neuroscience has generated transgenic rat and mouse models recapitulating the main pathological features of Alzheimer's disease such as neurofibrillary degeneration, neuroinflammation, synaptic failure, oxidative stress, and neurobehavioural changes. The models are used for preclinical efficacy studies with AXON active and passive vaccines, identification of novel diagnostic biomarkers in the cerebrospinal fluid and blood, and for development of anti-inflammatory AD therapy.

  • AXON bio-fluid diagnostic platform

    AXON animal models are critical for identification of potential diagnostic proteome and peptidome-based disease-specific biomarkers in cerebrospinal fluid.

  • AXON in-flame platform

    AXON animal models are ideally suited for validation of new drugs targeting specific inflammatory pathways involved in Alzheimer's disease.

AXON Frontotemporal lobar degeneration immunotherapy program

AXON Frontotemporal lobar degeneration immunotherapy program

An estimated 20% of patients affected by dementia suffer from Frontotemporal lobar degeneration (FTLD). Our preclinical studies showed that tau Achilles heel is involved in the pathogenesis of FTLD and thus represents a specific target for immunotherapy. AXON Neuroscience has launched a clinical trial on AADvac1 vaccine in patients suffering from non-fluent variant of nfvPPA.

Intellectual Property

AXON Neuroscience holds intellectual property rights:

  • to pathologically modified tau species derived from Alzheimer's disease brain tissues – the Alzheimer tau family – that directly correlate with the cognitive decline of AD patients
  • to the use of Alzheimer tau as a therapeutic drug target
  • to unique therapeutic and diagnostic antibodies, as well as their fragments, portions, and derivatives that bind specific regions of the Alzheimer tau protein responsible for the initiation and propagation of pathological tau-tau interactions
  • to methods of using these antibodies for diagnostics, prevention, and treatment of Alzheimer's disease and related human tauopathies
  • to antibodies and/or peptide vaccines that elicit an immune response directed to pathological tau proteins and tau deposits in patient brains
  • to transgenic non-human animal models expressing the Alzheimer tau protein

Publications

AXON Neuroscience has published a number of valuable original research papers in several prestigious scientific journals. The papers focus on structural neuroscience, neuroimmunology and neuroproteomics of Alzheimer's disease.

Therapeutic Visions

  • Safety and immunogenicity of the tau vaccine AADvac1 in patients with Alzheimer's disease: a randomised, double-blind, placebo-controlled, phase 1 trial
  • Novak P et al.
  • Lancet Neurology, 2016
  • Identification of structural determinants on tau protein essential for its pathological function: novel therapeutic target for tau immunotherapy in Alzheimer's disease
  • Kontsekova E, Zilka N, Kovacech B, Skrabana R, Novak M.
  • Alzheimers Res Ther. 2014 Aug 1;6(4):45.
  • First-in-man tau vaccine targeting structural determinants essential for pathological tau-tau interaction reduces tau oligomerisation and neurofibrillary degeneration in an Alzheimer's disease model
  • Kontsekova E, Zilka N, Kovacech B, Novak P, Novak M.
  • Alzheimers Res Ther. 2014 Aug 1;6(4):44.
  • Can we teach old dogs new tricks? Neuroprotective cell therapy in Alzheimer's and Parkinson's disease.
  • Kazmerova Z, Zilka N, Cente M, Neradil P, Zilkova M, Novak M.
  • J Alzheimers Dis. 2013; 37(2):251-72
  • Who fans the flames of Alzheimer's disease brains? Misfolded tau on the crossroad of neurodegenerative and inflammatory pathways
  • Zilka N, Kazmerova Z, Jadhav S, Neradil P, Madari A, Obetkova D, Bugos O, Novak M.
  • J Neuroinflamm. 2012; 9:47
  • Chaperone-Like Antibodies in Neurodegenerative Tauopathies: Implication for Immunotherapy
  • Kontsekova E, Ivanovova N, Handzusova M, Novak M.
  • Cell Mol Neurobiol. 2009; 29:793-798
  • Chaperone-like antibodies targeting misfolded tau protein: new vistas in the immunotherapy of neurodegenerative foldopathies
  • Zilka N, Kontsekova E, Novak M.
  • J Alzheimers Dis. 2008; 15(2):169-79.

Animal Models

  • Of rodents and men: the mysterious interneuronal pilgrimage of misfolded protein tau in Alzheimer’s disease.
  • Levarska L, Zilka N, Jadhav S, Neradil P, Novak M.
  • J Alzheimers Dis. 2013; 37(3):569-77
  • Immunomodulation of Memory-Impairing Protein Tau in Alzheimer's Disease
  • Zilka N, Stozicka Z, Kazmerova Z, Cente M, Kovacech B, Novak M.
  • Neurodegenerative Dis. 2012; 10:242-245
  • First transgenic rat model developing progressive cortical neurofibrillary tangles
  • Filipcik P, Zilka N, Bugos O, Kucerak J, Koson P, Novak P, Novak M.
  • Neurobiol Aging 2012; 33:1448-1456
  • Hyperphosphorylated truncated protein tau induces caspase 3 independent apoptotic-like pathway in the AD cellular model
  • Zilkova M, Zilka N, Kovac A, Kovacech B, Skrabana R, Skrabanova M, Novak M.
  • J Alzheimers Dis. 2011; 23:161-173
  • Genetic background modifies neurodegeneration and neuroinflammation driven by misfolded human tau protein in rat model of tauopathy: implication for immunomodulatory approach to Alzheimer's disease
  • Stozicka Z, Zilka N, Novak P, Kovacech B, Bugos O, Novak M.
  • J Neuroinflamm. 2010; 7:64
  • CSF phospho-tau correlates with behavioural decline and brain insoluble phospho-tau levels in a rat model of tauopathy
  • Zilka N, Korenova M, Kovacech B, Iqbal K, Novak M.
  • Acta Neuropath. 2010; 119:679-387
  • Misfolded tau protein and disease modifying pathways in transgenic rodent models of human tauopathies
  • Zilka N, Korenova M, Novak M.
  • Acta Neuropath. 2009; 118:71-86
  • Expression of a truncated human tau protein induces aqueous-phase free radicals in a rat model of tauopathy – implications for targeted antioxidative therapy
  • Cente M, Filipcik P, Mandakova S, Zilka N, Krajciova G, Novak M.
  • J Alzheimers Dis. 2009; 17:913-920
  • Beyond the rat models of human neurodegenerative disorders
  • Bugos O, Bhide M, Zilka N.
  • Cell Mol Neurobiol. 2009; 29:859-869
  • Memantine Prevents Sensitivity to Excitotoxic Cell Death of Rat Cortical Neurons Expressing Human Truncated Tau Protein
  • Cente M, Mandakova S, Filipcik P.
  • Cell Mol Neurobiol. 2009; 29:945-949
  • Cortical and Hippocampal Neurons from Truncated Tau Transgenic Rat Express Multiple Markers of Neurodegeneration
  • Filipcik P, Cente M, Krajciova G, Vanicky I, Novak M.
  • Cell Mol Neurobiol. 2009; 29:895-900
  • Human misfolded truncated tau protein promotes activation of microglia and leukocyte infiltration in the transgenic rat model of tauopathy
  • Zilka N, Stozicka Z, Kovac A, Pilipcinec E, Bugos O, Novak M.
  • J Neuroimmunol. 2009; 209 (1-2):16-25.
  • NeuroScale, the battery of behavioral tests with novel scoring system for phenotyping of transgenic rat model of tauopathy
  • Korenova M, Zilka N, Stozicka Z, Bugos O, Vanicky I, Novak M.
  • J Neurosci Methods. 2009; 177(1):108-14.
  • Truncated tau expression levels determine life span of a rat model of tauopathy without causing neuronal loss or correlating with terminal neurofibrillary tangle load
  • Koson P, Zilka N, Kovac A, Kovacech B, Korenova M, Filipcik P, Novak M.
  • Eur J Neurosci. 2008; 28(2):239-46.
  • Neurodegeneration caused by expression of human truncated tau leads to progressive neurobehavioural impairment in transgenic rats
  • Hrnkova M, Zilka N, Minichova Z, Koson P, Novak M.
  • Brain Res. 2007; 1130(1):206-13.
  • Expression of a truncated tau protein induces oxidative stress in a rodent model of tauopathy
  • Cente M, Filipcik P, Pevalova M, Novak M.
  • Eur J Neurosci. 2006; 24(4):1085-90.

Neuroprotemonics

  • N-terminal truncation of microtubule associated protein tau dysregulates its cellular localization
  • Paholikova K, Salingova B, Opattova A, Skrabana R, Majerova P, Zilka N, Kovacech B, Zilkova M, Barath P, Novak M.
  • J Alzheimers Dis. 2015;43(3):915-26.
  • Liquid chromatography-tandem mass spectrometry method for determination of panel of neurotransmitters in cerebrospinal fluid from the rat model for tauopathy
  • Kovac A, Somikova Z, Zilka N, Novak M.
  • Talanta. 2014 Feb;119:284-90.
  • Liquid Chromatography-Tandem Mass Spectrometry Method for Determination of Homocysteine in Rat Plasma: Application to the Study of a Rat Model for Tauopathies
  • Kovac A, Svihlova K, Michalicova A, Novak M.
  • J Chromatogr Sci. 2014 Dec 2.
  • Microglia display modest phagocytic capacity for extracellular tau oligomers.
  • Majerova P, Zilkova M, Kazmerova Z, Kovac A, Paholikova K, Kovacech B, Zilka N, Novak M.
  • J Neuroinflammation. 2014 Sep 13;11(1):161.
  • Liquid chromatography-tandem mass spectrometry method for determination of panel of neurotransmitters in cerebrospinal fluid from the rat model for tauopathy
  • Kovac A, Somikova Z, Zilka N, Novak M.
  • Talanta. 2014; 119:284-90
  • Protein truncation as a common denominator of human neurodegenerative foldopathies.
  • Jadhav S, Zilka N, Novak M.
  • Mol Neurobiol. 2013; 48(3):516-32
  • Intracellular degradation of misfolded tau protein induced by geldanamycin is associated with activation of proteasome
  • Opattova A, Filipcik P, Cente M, Novak M.
  • J Alzheimers Dis. 2013; 33(2):339-48.
  • The self-perpetuating tau truncation circle
  • Zilka N, Kovacech B, Barath P, Kontsekova E, Novak M.
  • Biochem Soc Trans. 2012; 40:681-686
  • Crystallization and preliminary X-ray diffraction analysis of two peptides from Alzheimer PHF in complex with the MN423 antibody Fab fragment
  • Skrabana R, Cehlar O, Flachbartova Z, Kovac A, Sevcik J, Novak M.
  • Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012; 68(Pt 10):1186-90.
  • Crystallization and preliminary X-ray diffraction analysis of tau protein microtubule-binding motifs in complex with Tau5 and DC25 antibody Fab fragments
  • Cehlar O, Skrabana R, Kovac A, Kovacech B, Novak M.
  • Acta Crystallogr Sect F Struct Biol Cryst Commun. 2012; 68(Pt 10):1181-5.
  • Misfolded Truncated Protein tau Induces Innate Immune Response via MAPK Pathway
  • Kovac A, Zilka N, Kazmerova Z, Cente M, Zilkova M, Novak M.
  • J Immunol. 2011; 187:2732-2739
  • Tau Truncation is a Productive Posttranslational Modification of Neurofibrillary Degeneration in Alzheimer's Disease
  • Kovacech B, Novak M.
  • Curr Alz Res. 2010; 7: 708-716
  • Monoclonal antibody MN423 as a stable mold facilitates structure determination of disordered tau protein
  • Skrabana R, Dvorsky R, Sevcik J, Novak M.
  • J Struct Biol. 2010; 171: 74-81
  • Transition of Tau Protein from Disordered to Misordered in Alzheimer's Disease
  • Kovacech B, Skrabana R, Novak M.
  • Neurodegenerative Dis. 2010; 7:24-27
  • New age of neuroproteomics in Alzheimer's disease research
  • Kovacech B, Zilka N, Novak M.
  • Cell Mol Neurobiol. 2009; 29:799-805
  • Structure solution of misfolded conformations adopted by intrinsically disordered Alzheimer's tau protein
  • Sevcik J, Skrabana R, Kontsekova E, Novak M.
  • Protein Pept Lett. 2009; 16(1):61-4.
  • Rat tau proteome consists of six tau isoforms: Implication for animal models of human tauopathies
  • Hanes J, Zilka N, Bartkova M, Caletkova M, Dobrota D, Novak M.
  • J Neurochem. 2009; 108, 1167–1176.
  • Preserving free thiols of intrinsically disordered tau protein without the use of a reducing agent
  • Krajciova G, Skrabana R, Filipcik P, Novak M.
  • ANALYTICAL BIOCHEMISTRY. 2008; 383(2):343-345.
  • High-yield purification of fetal tau preserving its structure and phosphorylation pattern
  • Ivanovova N, Handzusova M, Hanes J, Kontsekova E, Novak M.
  • J Immunol Methods. 2008; 339(1):17-22.
  • X-ray structure of the PHF core C-terminus: insight into the folding of the intrinsically disordered protein tau in Alzheimer's disease
  • Sevcik J, Skrabana R, Dvorsky R, Csokova N, Iqbal K, Novak M.
  • FEBS Lett. 2007; 581(30):5872-8.
  • A novel monoclonal antibody DC63 reveals that inhibitor 1 of protein phosphatase 2A is preferentially nuclearly localised in human brain
  • Kovacech B, Kontsekova E, Zilka N, Novak P, Skrabana R, Filipcik P, Iqbal K, Novak M.
  • FEBS Lett. 2007; 581(4):617-22.
  • Preparation, crystallization and preliminary X-ray analysis of the Fab fragment of monoclonal antibody MN423, revealing the structural aspects of Alzheimer's paired helical filaments
  • Csokova N, Skrabana R, Urbanikova L, Kovacech B, Sevcik J, Novak M.
  • Protein Pept Lett. 2006; 13(9):941-4.
  • Alzheimer's-disease-associated conformation of intrinsically disordered tau protein studied by intrinsically disordered protein liquid-phase competitive enzyme-linked immunosorbent assay
  • Skrabana R, Skrabanova-Khuebachova M, Kontsek P, Novak M.
  • Anal Biochem. 2006; 359(2):230-7.
  • Intrinsically disordered proteins in the neurodegenerative processes: formation of tau protein paired helical filaments and their analysis
  • Skrabana R, Sevcik J, Novak M.
  • Cell Mol Neurobiol. 2006; 26(7-8):1085-97.
  • First insert of tau protein is present in all stages of tau pathology in Alzheimer's disease
  • Soltys K, Rolkova G, Vechterova L, Filipcik P, Zilka N, Kontsekova E, Novak M.
  • Neuroreport. 2005; 16(15):1677-81.
  • Alzheimer paired helical filaments (PHFs) studied by high-resolution TEM: what can vertical Pt-C replication tell us about the organization of the pronase-digested PHF core?
  • Ruben GC, Novak M, Edwards PC, Iqbal K.
  • Microsc Res Tech. 2005; 67(3-4):196-209.
  • Folding of Alzheimer's core PHF subunit revealed by monoclonal antibody 423
  • Skrabana R, Kontsek P, Mederlyova A, Iqbal K, Novak M.
  • FEBS Lett. 2004; 568(1-3):178-82.
  • Rapid purification of truncated tau proteins: model approach to purification of functionally active fragments of disordered proteins, implication for neurodegenerative diseases
  • Csokova N, Skrabana R, Liebig HD, Mederlyova A, Kontsek P, Novak M.
  • Protein Expr Purif. 2004; 35(2):366-72.
  • DC11: a novel monoclonal antibody revealing Alzheimer's disease-specific tau epitope
  • Vechterova L, Kontsekova E, Zilka N, Ferencik M, Ravid R, Novak M.
  • Neuroreport. 2003 Jan 20;14(1):87-91.
  • Mapping the C terminal epitope of the Alzheimer's disease specific antibody MN423
  • Khuebachova M, Verzillo V, Skrabana R, Ovecka M, Vaccaro P, Panni S, Bradbury A, Novak M.
  • J Immunol Methods. 2002 Apr 1;262(1-2):205-15.