460
Views
0
CrossRef citations to date
0
Altmetric
Drug Evaluation

Masitinib for the Treatment of Alzheimer’s Disease

ORCID Icon, , , , , & ORCID Icon show all
Pages 263-276 | Received 03 May 2021, Accepted 08 Aug 2021, Published online: 20 Aug 2021

References

  • Le Cesne A , BlayJ-Y, BuiBNet al. Phase II study of oral masitinib mesilate in imatinib-naïve patients with locally advanced or metastatic gastro-intestinal stromal tumor (GIST). Eur. J. Cancer, 46(8), 1344–1351 (2010).
  • Adenis A , BlayJ-Y, Bui-NguyenBet al. Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial. Ann. Oncol., 25(9), 1762–1769 (2014).
  • Dubreuil P , LetardS, CiufoliniMet al. Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS ONE, 4(9), e7258 (2009).
  • Marech I , PatrunoR, ZizzoNet al. Masitinib (AB1010), from canine tumor model to human clinical development: where we are? Crit. Rev. Oncol. Hematol., 91(1), 98–111 (2014).
  • Demetri GD . Differential properties of current tyrosine kinase inhibitors in gastrointestinal stromal tumors. Semin. Oncol., 38, S10–S19 (2011).
  • Soria JC , MassardC, MagnéNet al. Phase 1 dose-escalation study of oral tyrosine kinase inhibitor masitinib in advanced and/or metastatic solid cancers. Eur. J. Cancer, 45(13), 2333–2341 (2009).
  • Aljoundi AK , AgoniC, OlotuFA, SolimanME. ‘Piperazining’ the catalytic gatekeepers: unraveling the pan-inhibition of SRC kinases; LYN, FYN and BLK by masitinib. Future Med. Chem., 11(18), 2365–2380 (2019).
  • Shirazi SK , WoodJG. The protein tyrosine kinase, fyn, in Alzheimer’s disease pathology. Neuroreport, 4(4), 435–437 (1993).
  • Lee G , ThangavelR, SharmaVMet al. Phosphorylation of tau by fyn: implications for Alzheimer’s disease. J. Neurosci., 24(9), 2304–2312 (2004).
  • Tebib J , MarietteX, BourgeoisPet al. Masitinib in the treatment of active rheumatoid arthritis: results of a multicenter, open-label, dose-ranging, Phase IIa study. Arthritis Res. Ther., 11(3), R95 (2009).
  • AB Science announces that Phase IIb/III study evaluating oral in Alzheimer’s disease met its primary endpoint. (2020). https://www.globenewswire.com/news-release/2020/12/16/2145869/0/en/AB-Science-announces-that-Phase-2B-3-study-evaluating-oral-in-Alzheimer-s-disease-met-its-primary-endpoint.html
  • Li T , MartinE, AbadaYSet al. Effects of chronic masitinib treatment in APPswe/PSEN1dE9 transgenic mice modeling Alzheimer’s disease. J. Alzheimers Dis., 76(4), 1339–1345 (2020).
  • Lonskaya I , HebronML, SelbySTet al. Nilotinib and bosutinib modulate pre-plaque alterations of blood immune markers and neuro-inflammation in Alzheimer’s disease models. Neuroscience, 24(304), 316–327 (2015).
  • Lonskaya I , HebronML, DesforgesNM, FranjieA, MoussaCE. Tyrosine kinase inhibition increases functional parkin-Beclin-1 interaction and enhances amyloid clearance and cognitive performance. EMBO Mol. Med., 5(8), 1247–1262 (2013).
  • Cummings J , LeeG, RitterA, SabbaghM, ZhongK. Alzheimer’s disease drug development pipeline: 2020. Alzheimers Dement (N Y)., 6(1), e12050 (2020).
  • Cummings JL , TongG, BallardC. Treatment combinations for Alzheimer’s disease: current and future pharmacotherapy options. J. Alzheimer’s Dis., 67(3), 779–794 (2019).
  • Cummings J , FeldmanHH, ScheltensP. The ‘rights’ of precision drug development for Alzheimer’s disease. Alzheimers Res. Ther., 11(1), 76 (2019).
  • Sandhu JK , KulkaM. Decoding mast cell-microglia communication in neurodegenerative diseases. Int. J. Mol. Sci., 22, 1093 (2021).
  • Skaper SD , FacciL, KeeWJ, StrijbosPJ. Potentiation by histamine of synaptically mediated excitotoxicity in cultured hippocampal neurones: a possible role for mast cells. J. Neurochem., 76(1), 47–55 (2001).
  • Skaper S , GiustiP, FacciL. Microglia and mast cells: two tracks on the road to neuroinflammation. FASEB J., 26(8), 3103–3117 (2012).
  • Skaper S , FacciL, GiustiP. Mast cells, glia and neuroinflammation: partners in crime?Immunology, 141(3), 314–327 (2014a).
  • Skaper SD , FacciL, GiustiP. Neuroinflammation, microglia and mast cells in the pathophysiology of neurocognitive disorders: a review. CNS Neurol. Disord. Drug Targets, 13(10), 1654–1666 (2014b).
  • Skaper SD . Mast cell-glia dialogue in chronic pain and neuropathic pain: blood-brain barrier implications. CNS Neurol. Disord. Drug Targets, 15(9), 1072–1078 (2016).
  • Anastassiadis T , DeaconSW, DevarajanKet al. Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat. Biotechnol., 29(11), 1039–1045 (2011).
  • Tang SJ , Fesharaki-ZadehA, TakahashiHet al. Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy. Acta Neuropathol. Commun., 8(1), 96 (2020).
  • Liu G , FiockKL, LevitesYet al. Fyn depletion ameliorates tau(P301L)-induced neuropathology. Acta Neuropathol. Commun., 8(1), 108 (2020).
  • Chin J , PalopJJ, PuoliväliJet al. Fyn kinase induces synaptic and cognitive impairments in a transgenic mouse model of Alzheimer’s disease. J. Neurosci., 25(42), 9694–9703 (2005).
  • Roberson ED , HalabiskyB, YooJWet al. Amyloid-β/Fyn-induced synaptic, network, and cognitive impairments depend on tau levels in multiple mouse models of Alzheimer’s disease. J. Neurosci., 31(2), 700–711 (2011).
  • Tang SJ , Fesharaki-ZadehA, TakahashiHet al. Fyn kinase inhibition reduces protein aggregation, increases synapse density and improves memory in transgenic and traumatic Tauopathy. Acta Neuropathol. Commun., 8(1), 96 (2020).
  • Tezuka T , UmemoriH, AkiyamaTet al. PSD-95 promotes Fyn-mediated tyrosine phosphorylation of the N-methyl-D-aspartate receptor subunit NR2A. Proc. Natl Acad. Sci. USA, 96, 435–440 (1999).
  • Trepanier CH , JacksonMF, MacDonaldJF. Regulation of NMDA receptors by the tyrosine kinase Fyn. FEBS J., 279, 12–19 (2012).
  • Dementia . http://www.who.int/news-room/fact-sheets/detail/dementia
  • 2021 Alzheimer’s disease facts and figures. Alzheimers Dement., 17(3), 327–406(2021).
  • Ittner LM , KeYD, DelerueF, BiMet al. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell, 142, 387–397 (2010).
  • Lopes S , Vaz-SilvaJ, PintoVet al. Tau protein is essential for stress-induced brain pathology. Proc. Natl Acad. Sci. USA, 113(26), E3755–3763 (2016).
  • Kong C , XieH, GaoZet al. Binding between prion protein and abeta oligomers contributes to the pathogenesis of Alzheimer’s disease. Virol. Sin., 34, 475–488 (2019).
  • Dubreuil P , LetardS, CiufoliniMet al. Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PloS ONE, 4, e7258 (2009).
  • Williamson R , ScalesT, ClarkBRet al. Rapid tyrosine phosphorylation of neuronal proteins including tau and focal adhesion kinase in response to amyloid-beta peptide exposure: involvement of Src family protein kinases. J. Neurosci., 22(1), 10–20 (2002).
  • Nygaard HB . Targeting Fyn kinase in Alzheimer’s disease. Biol. Psychiatry, 83, 369–376 (2018).
  • ClinicalTrial.gov . Masitinib in patients with mild-to-moderate Alzheimer’s disease. (2020). https://clinicaltrials.gov/ct2/show/NCT01872598
  • AB Science press release. (2020). https://www.ab-science.com/results-from-phase-2b-3-studyevaluating-masitinib-in-alzheimers-disease/
  • Yasunaga M , YagiT, HanzawaNet al. Involvement of Fyn tyrosine kinase in progression of cytokinesis of B lymphocyte progenitor. J. Cell Biol., 132(1–2), 91–99 (1996).
  • Bellamy F , BaderT, MoussyA, HermineO. Pharmacokinetics of masitinib in cats. Vet. Res. Commun., 33(8), 831–837 (2009).
  • Harcha PA , GarcésP, ArredondoC, FernándezG, SáezJC, van ZundertB. Mast cell and astrocyte hemichannels and their role in Alzheimer’s disease, ALS, and harmful stress conditions. International J. Mol. Sci., 22(4), 1924 (2021).
  • Harcha PA , VargasA, YiC, KoulakoffAA, GiaumeC, SáezJC. Hemichannels are required for amyloid β-peptide-induced degranulation and are activated in brain mast cells of APPswe/PS1dE9 mice. J. Neurosci., 35(25), 9526–9538 (2015).
  • Jones MK , NairA, GuptaM. Mast cells in neurodegenerative disease. Front. Cell Neurosci., 13, 171 (2019).
  • Motta C , FinardiA, TonioloSet al. Protective role of cerebrospinal fluid inflammatory cytokines in patients with amnestic mild cognitive impairment and early Alzheimer’s disease carrying apolipoprotein E4 genotype. J. Alzheimers Dis., 76(2), 681–689 (2020).
  • Skaper SD , FacciL, ZussoM, GiustiP. An inflammation-centric view of neurological disease: beyond the neuron. Front. Cell Neurosci., 12, 72 (2018).
  • Hendriksen E , van BergeijkD, OostingRS, RedegeldFA. Mast cells in neuroinflammation and brain disorders. Neurosci. Biobehav. Rev., 79, 119–133 (2017).
  • Shaik-Dasthagirisaheb YB , ContiP. The role of mast cells in Alzheimer’s disease. Adv. Clin. Exp. Med., 25(4), 781–787 (2016).
  • Sweeney MD , SagareAP, ZlokovicBV. Blood-brain barrier breakdown in Alzheimer disease and other neurodegenerative disorders. Nat. Rev. Neurol., 14(3), 133–150 (2018).
  • Lee G , ThangavelR, SharmaVMet al. Phosphorylation of tau by fyn: implications for Alzheimer’s disease. J. Neurosci., 24(9), 2304–2312 (2004).
  • Williamson R , ScalesT, ClarkBRet al. Rapid tyrosine phosphorylation of neuronal proteins including tau and focal adhesion kinase in response to amyloid-beta peptide exposure: involvement of Src family protein kinases. J. Neurosci., 22(1), 10–20 (2002).
  • Briner A , GötzJ, PolancoJC. Fyn kinase controls Tau aggregation in vivo. Cell Rep., 32(7), 108045 (2020).
  • Sette C , ParonettoMP, BarchiM, BevilacquaA, GeremiaR, RossiP. Tr-kit-induced resumption of the cell cycle in mouse eggs requires activation of a Src-like kinase. EMBO J., 21(20), 5386–5395 (2002).
  • Folch J , JunyentF, VerdaguerEet al. Role of cell cycle re-entry in neurons: a common apoptotic mechanism of neuronal cell death. Neurotox. Res., 22(3), 195–207 (2012).
  • Seward ME , SwansonE, NorambuenaAet al. Amyloid-β signals through tau to drive ectopic neuronal cell cycle re-entry in Alzheimer’s disease. J. Cell Sci., 126(Pt 5), 1278–1286 (2013).
  • Esposito Z , BelliL, TonioloSet al. Amyloid beta, glutamate, excitotoxicity in Alzheimer’s disease: are we on the right track? CNS Neurosci. Ther., 19(8), 549–555 (2013).
  • Souter S , LeeG. Tubulin-independent tau in Alzheimer’s disease and cancer: implications for disease pathogenesis and treatment. Curr. Alzheimer Res., 7(8), 697–707 (2010).
  • Piccioni G , MangoD, SaidiA, CorboM, NisticòR. Targeting microglia-synapse interactions in Alzheimer’s disease. Int. J. Mol. Sci., 22(5), 2342 (2021).
  • Ittner LM , GötzJ. Amyloid-β and tau – a toxic pas de deux in Alzheimer’s disease. Nat. Rev. Neurosci., 12(2), 65–72 (2011).
  • Elmore MR , NajafiAR, KoikeMAet al. Colony-stimulating factor 1 receptor signaling is necessary for microglia viability, unmasking a microglia progenitor cell in the adult brain. Neuron, 82, 380–397 (2014).
  • Trias E , IbarburuS, Barreto-NunezRet al. Post-paralysis tyrosine kinase inhibition with masitinib abrogates neuroinflammation and slows disease progression in inherited amyotrophic lateral sclerosis. J. Neuroinflammation, 13, 177 (2016).
  • De Sousa VL , AraújoSB, AntonioLMet al. Innate immune memory mediates increased susceptibility to Alzheimeŕs disease-like pathology in sepsis surviving mice. Brain Behav. Immun., 7, S0889-1591(21)00158-6 (2021).
  • Marzan DE , Brügger-VerdonV, WestBLet al. Activated microglia drive demyelination via CSF1R signaling. Glia, 69(6), 1583–1604 (2021).
  • Son Y , JeongYJ, ShinNRet al. Inhibition of colony-stimulating factor 1 receptor by PLX3397 prevents amyloid beta pathology and rescues dopaminergic signaling in aging 5xFAD mice. Int. J. Mol. Sci., 21(15), 5553 (2020).
  • Wang CF , ZhaoCC, LiuWLet al. Depletion of microglia attenuates dendritic spine loss and neuronal apoptosis in the acute stage of moderate traumatic brain injury in mice. J. Neurotrauma, 37(1), 43–54 (2020).
  • Boros BD , GreathouseKM, GentryEGet al. Dendritic spines provide cognitive resilience against Alzheimer’s disease. Ann. Neurol., 82(4), 602–614 (2017).
  • Boros BD , GreathouseKM, GearingMet al. Dendritic spine remodeling accompanies Alzheimer’s disease pathology and genetic susceptibility in cognitively normal aging. Neurobiol. Aging, 73, 92–103 (2019).
  • Walker CK , HerskowitzJH. Dendritic spines: mediators of cognitive resilience in aging and Alzheimer’s disease. Neuroscientist1073858420945964 (2020).
  • Dumitriu D , HaoJ, HaraYet al. Selective changes in thin spine density and morphology in monkey prefrontal cortex correlate with aging-related cognitive impairment. J. Neurosci., 30(22), 7507–7515 (2010).
  • Lambert MP , BarlowAK, ChromyBAet al. Diffusible, nonfibrillar ligands derived from Abeta1-42 are potent central nervous system neurotoxins. Proc. Natl Acad. Sci. USA, 95(11), 6448–6453 (1998).
  • Suzuki T , Okumura-NojiK. NMDA receptor subunits epsilon 1 (NR2A) and epsilon 2 (NR2B) are substrates for Fyn in the postsynaptic density fraction isolated from the rat brain. Biochem. Biophys. Res. Commun., 216, 582–588 (1995).
  • Nakazawa T , KomaiS, TezukaTet al. Characterization of Fyn-mediated tyrosine phosphorylation sites on GluR epsilon 2 (NR2B) subunit of the N-methyl-D-aspartate receptor. J. Biol. Chem., 276, 693–699 (2001).
  • Haas LT , SalazarSV, KostylevMAet al. Metabotropic glutamate receptor 5 couples cellular prion protein to intracellular signaling in Alzheimer’s disease. Brain, 139(Pt 2), 526–546 (2016).
  • Hermine O . Masitinib for the treatment of Alzheimer’s disease: clinical and preclinical data. Neurobiol. Aging, 39, S1eS13 (2016).
  • Ma QL , YangF, FrautschySA, ColeGM. PAK in Alzheimer disease, Huntington disease and X-linked mental retardation. Cell Logist., 2(2), 117–125 (2012).
  • Ittner LM , KeYD, DelerueFet al. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell, 142(3), 387–397 (2010).
  • Haass C , MandelkowE. Fyn-tau-amyloid: a toxic triad. Cell, 142(3), 356–358 (2010).
  • Kaufman AC , SalazarSV, HaasLTet al. Fyn inhibition rescues established memory and synapse loss in Alzheimer mice. Ann. Neurol., 77(6), 953–971 (2015).
  • Lee G , NewmanST, GardDL, BandH, PanchamoorthyG. Tau interacts with src-family non-receptor tyrosine kinases. J. Cell Sci., 111(Pt 21), 3167–3177 (1998).
  • Barry AE , KlyubinI, McDonald JMet al. Alzheimer’s disease brain-derived amyloid-beta-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein. J. Neurosci., 31, 7259–7263 (2011).
  • Minami SS , CliffordTG, HoeHSet al. Fyn knock-down increases Abeta, decreases phospho-tau, and worsens spatial learning in 3Tg-AD mice. Neurobiol. Aging, 33(4), 825.e15–24 (2012).
  • Babus LW , LittleEM, KeenoyKEet al. Decreased dendritic spine density and abnormal spine morphology in Fyn knockout mice. Brain Res., 1415, 96–102 (2011).
  • Toniolo S , SenA, HusainM. Modulation of brain hyperexcitability: potential new therapeutic approaches in Alzheimer’s disease. Int. J. Mol. Sci., 21(23), 9318 (2020).
  • Piette F , BelminJ, VincentHet al. Masitinib as an adjunct therapy for mild-to-moderate Alzheimer’s disease: a randomised, placebo-controlled Phase 2 trial. Alzheimers. Res. Ther., 3(2), 16 (2011).
  • Trias E , IbarburuS, Barreto-NúñezRet al. Evidence for mast cells contributing to neuromuscular pathology in an inherited model of ALS. Insight, 2(20), e95934 (2017).
  • Trias E , KingPH, SiY, KwonYet al. Mast cells and neutrophils mediate peripheral motor pathway degeneration in ALS. JCI Insight, 3(19), e123249 (2018).
  • Niederhoffer N , LevyR, SickEet al. Amyloid beta peptides trigger CD47-dependent mast cell secretory and phagocytic responses. Int. J. Immunopathol. Pharmacol., 22(2), 473–483 (2009).
  • Fagiani F , LanniC, RacchiM, GovoniS. Targeting dementias through cancer kinases inhibition. Alzheimers Dement. (NY), 6(1), e12044 (2020).
  • Nygaard HB , WagnerAF, BowenGSet al. A Phase Ib multiple ascending dose study of the safety, tolerability, and central nervous system availability of AZD0530 (saracatinib) in Alzheimer’s disease. Alzheimers Res. Ther., 7(1), 35 (2015).
  • Van Dyck CH , NygaardHB, ChenKet al. Effect of AZD0530 on cerebral metabolic decline in Alzheimer disease: a randomized clinical trial. JAMA Neurol., 76(10), 1219–1229 (2019).
  • Calabrò M , RinaldiC, SantoroG, CrisafulliC. The biological pathways of Alzheimer disease: a review. AIMS Neurosci., 8(1), 86–132 (2020).
  • Ray WJ , Buggia-PrevotV. Novel targets for Alzheimer’s disease: a view beyond amyloid. Annu. Rev. Med., 72, 15–28 (2021).
  • Xiao S , ChanP, WangTet al. A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase III clinical trial of sodium oligomannate for mild-to-moderate Alzheimer’s dementia. Alzheimers Res Ther., 13(1), 62 (2021).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.