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LENIT publications and patents

Published on 7 June 2022

1- Importance of modelling brain and blood-brain barrier in drug discovery

a. Pavoni S, Jarray R, Nassor F, Guyot AC, Cottin S, Rontard J, Mikol J, Mabondzo A, Deslys JP, Yates F. (2018). Small-molecule induction of Aβ-42 peptide production in human cerebral organoids to model Alzheimer's disease associated phenotypes. PLoS One. 13(12): e0209150

b. Le Roux G, Jarray R, Guyot AC, Pavoni S , Costa N , Théodoro F , Nassor F, Pruvost A , Tournier N , Kiyan Y , Langer O , Yates F, Deslys JP , Mabondzo A. Proof-of-Concept Study of Drug Brain Permeability Between in Vivo Human Brain and an in Vitro iPSCs-Human Blood-Brain Barrier Model. Sci Rep. 2019;9(1):16310. Published 2019 Nov 5. doi:10.1038/s41598-019-52213-6

c. Lacombe O, Videau O, Chevillon D, Guyot AC, Contreras C, Blondel S, Nicolas L, Ghettas A, Benech H, Thevenot E, Pruvost A, Bolze S, Krzaczkowski L, Prevost C, and Mabondzo A. 2011. 'In Vitro Primary Human and Animal Cell-Based Blood-Brain Barrier Models as a Screening Tool in Drug Discovery', Molecular Pharmaceutics, 2011, 8: 651-63. doi: 10.1021/mp1004614. Epub 2011 Apr 15. PMID:21438632.

d. Mabondzo A, Bottlaender M, Guyot AC, Tsaouin K, Deverre JR, Balimane PV. Validation of in vitro cell-based human blood-brain barrier model using clinical positron emission tomography radioligands to predict in vivo human brain penetration.Mol Pharm. 2010, 7(5):1805-15. doi: 10.1021/mp1002366. Epub 2010 Sep 15. PMID:20795735.

e. Mathieu C, Sii-Fekice K, Fouchet P, Etienne O, Haton C, Mabondzo A, Boussin F, Mouthon MA (2008). Brain endothelial cells induce quiescence of neural stem/progenitor cells through BMP/Smad pathway and upregulation of PTEN levels within the SVZ niche. Cellular and Molecular Neuroscience 38(4):569-77.

f. Josserand V, Pélerin H, de Bruin B, Jego B, Kuhnast B, Hinnen F, Ducongé F, Boisgard R, Beuvon F, Chassoux F, Daumas-Duport C, Ezan E, Dollé F, Mabondzo A, Tavitian B. Evaluation of drug penetration into the brain: a double study by in vivo imaging with positron emission tomography and using an in vitro model of the human blood-brain barrier.J Pharmacol Exp Ther. 2006, 16(1):79-86. Epub 2005 Oct 6. PMID: 16210395.

g. Garberg P, Ball M, Borg N, Cecchelli R, Fenart L, Hurst RD, Lindmark T, Mabondzo A, Nilsson JE, Raub TJ, Stanimirovic D, Terasaki T, Oberg JO, Osterberg T. In vitro models for the blood-brain barrier. Toxicol In Vitro. 2005, 19(3):299-334.PMID 15713540.

h. Didier N., Romero IA., Créminon C., Wijkhuisen A., Grassi J., Mabondzo A. (2003). Secretion of Interleukin-1b by astrocytes mediates endothelin-1 and Tumor necrosis factor-alpha effects on human brain microvascular endothelial cell permeability. J Neurochem 86 (1) 246-254.

i. Megard I, Garrigues A, Orlowski S, Jorajuria S, Clayette P, Ezan E, Mabondzo A. A co-culture-based model of human blood-brain barrier: application to active transport of indinavir and in vivo-in vitro correlation.Brain Res. 2002, 927(2):153-67. PMID: 118210.

2- Blood-brain barrier dysfunction and environmental exposure on the adult and developing brains

a. Disdier C, Chalansonnet M, Gagnaire F, Gaté L, Cosnier F, Devoy J, Saba W, Lund AK, Brun E, Mabondzo A. Brain Inflammation, Blood Brain Barrier dysfunction and Neuronal Synaptophysin Decrease after Inhalation Exposure to Titanium Dioxide Nano-aerosol in Aging Rats. Sci Rep. 2017, 7(1):12196. doi: 10.1038/s41598-017-12404-5. PMID:28939873.

b. Gaté L, Disdier C, Cosnier F, Gagnaire F, Devoy J, Saba W, Brun E, Chalansonnet M, Mabondzo A. Biopersistence and translocation to extrapulmonary organs of titanium dioxide nanoparticles after subacute inhalation exposure to aerosol in adult and elderly rats.Toxicol Lett. 2017, 265:61-69. doi: 10.1016/j. PMID:27865850.

c. Disdier C, Devoy J, Cosnefroy A, Chalansonnet M, Herlin-Boime N, Brun E, Lund A, Mabondzo A. Tissue biodistribution of intravenously administrated titanium dioxide nanoparticles revealed blood-brain barrier clearance and brain inflammation in rat. Part Fibre Toxicol. 2015 Sep 4;12:27. doi: 10.1186/s12989-015-0102-8. PMID:26337446

d. Oppenheim HA, Lucero J, Guyot AC, Herbert LM, McDonald JD, Mabondzo A, Lund AK. Exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice. Part Fibre Toxicol. 2013;10:62. doi: 10.1186/1743-8977-10-62. PMID: 24344990.

e. Brun E, Carrière M, Mabondzo A. In vitro evidence of dysregulation of blood-brain barrier function after acute and repeated/long-term exposure to TiO(2) nanoparticles.Biomaterials. 2012, 33(3):886-96. doi: 10.1016/j.biomaterials. PMID: 22027597

3- Blood-brain barrier physiology - Drug transporters and neuroinflammation
a. Harati R, Benech H, Villégier AS, Mabondzo A. P-glycoprotein, breast cancer resistance protein, Organic Anion Transporter 3, and Transporting Peptide 1a4 during blood-brain barrier maturation: involvement of Wnt/β-catenin and endothelin-1 signaling. Mol Pharm. 2013, 6;10(5):1566-80. doi: 10.1021/mp300334r. PMID:22998451.

b. Soares RV, Do TM, Mabondzo A, Pons G, Chhun S. Ontogeny of ABC and SLC transporters in the microvessels of developing rat brain. Fundam Clin Pharmacol. 2016,30(2):107-16. doi: 10.1111/fcp.12175. PMID: 26662930

c. Mathieu C, Sii-Felice K, Fouchet P, Etienne O, Haton C, Mabondzo A, Boussin FD, Mouthon MA. Endothelial cell-derived bone morphogenetic proteins control proliferation of neural stem/progenitor cells. Mol Cell Neurosci. 2008, 38(4):569-77. doi: 10.1016/j.mcn.2008.05.005. PMID:18583149

d. Harati R, Villégier AS, Banks WA, Mabondzo A. Susceptibility of juvenile and adult blood-brain barrier to endothelin-1: regulation of P-glycoprotein and breast cancer resistance protein expression and transport activity.J Neuroinflammation. 2012, 9:273. doi: 10.1186/1742-2094-9-273. PMID: 23253775.

e. Hembury A, Mabondzo A. Endothelin-1 reduces p-glycoprotein transport activity in an in vitro model of human adult blood-brain barrier. Cell Mol Neurobiol. 2008, 28(7):915-21. doi: 10.1007/s10571-008-9277-y.PMID:18379872.

f. Théron D, Barraud de Lagerie S, Tardivel S, Pélerin H, Demeuse P, Mercier C, Mabondzo A, Farinotti R, Lacour B, Roux F, Gimenez F.Influence of tumor necrosis factor-alpha on the expression and function of P-glycoprotein in an immortalised rat brain capillary endothelial cell line, GPNT. Biochem Pharmacol. 2003, 15; 66(4):579-87.PMID: 12906922.

g. Didier N, Romero IA, Créminon C, Wijkhuisen A, Grassi J, Mabondzo A. Secretion of interleukin-1beta by astrocytes mediates endothelin-1 and tumour necrosis factor-alpha effects on human brain microvascular endothelial cell permeability. J Neurochem. 2003, 86(1):246-54.PMID: 12807444.

h. Didier N, Banks WA, Créminon C, Dereuddre-Bosquet N, Mabondzo A. HIV-1-induced production of endothelin-1 in an in vitro model of the human blood-brain barrier. Neuroreport. 2002 Jul 2;13(9):1179-83. PMID:12151765.

4- Neuroprotective anti-inflammatory strategies to prevent Tau phosphorylation and cognitive deficit

a. Guyot AC, Leuxe C, Disdier C, Le Roux G, Jaumain E, Costa N, Oumata N, Gallons H, Meijer L, Charbonnier JB, Lund A and Mabondzo A. Small Purine Derivative Compound Crossing the Blood-Brain Barrier, a Putative Target of Prohibitin with Potential Interest for Cognitive Deficit Rescue in Aging mice and Tau pathology Treatment. Scientific Report, September 2019

b. Portelius E, Durieu E, Bodin M, Cam M, Pannee J, Leuxe C, Mabondzo A, Oumata N, Galons H, Lee JY, Chang YT, Stϋber K, Koch P, Fontaine G, Potier MC, Manousopoulou A, Garbis SD, ; Zetterberg H, Meijer L (2016). Specific Triazine Herbicides Induce Amyloid-β42 Production.J Alzheimers Dis. 54(4):1593-1605

5- Drug discovery and delivery 

a. Ullio-Gamboa G, Udobi KC, Dezard S, Perna MK, Miles KN, Costa N, Taran F, Pruvost A, Benoit JP, Skelton MR, Lonlay P, Mabondzo A. Dodecyl creatine ester-loaded nanoemulsion as a promising therapy for creatine transporter deficiency. Nanomedicine (Lond). 2019, 14(12):1579-1593. doi: 10.2217/nnm-2019-0059. PMID:31038003. 

b. Udobi KC, Kokenge AN, Hautman ER, Ullio G, Coene J, Williams MT, Vorhees CV, Mabondzo A, Skelton MR (2018). Cognitive deficits and increases in creatine precursors in a brain-specific knockout of the creatine transporter gene Slc6a8. Genes Brain Behav. 17(6):e12461.

c. Trotier-Faurion A, Passirani C, Béjaud J, Dézard S, Valayannopoulos V, Taran F, de Lonlay P, Benoit JP, Mabondzo A. Dodecyl creatine ester and lipid nanocapsule: a double strategy for the treatment of creatine transporter deficiency. Nanomedicine (Lond). 2015, 10(2):185-91. doi: 10.2217/nnm.13.205. PMID:24559037

d. Trotier-Faurion A, Dézard S, Taran F, Valayannopoulos V, de Lonlay P, Mabondzo A. Synthesis and biological evaluation of new creatine fatty esters revealed dodecyl creatine ester as a promising drug candidate for the treatment of the creatine transporter deficiency. J Med Chem. 2013, 56(12):5173-81. doi: 10.1021/jm400545n. PMID:23697594.

e. Niu Z, Samaridou E, Jaumain E, Coëne J, Ullio G, Shrestha N, Garcia J, Durán-Lobato M, Tovar S, Santander-Ortega MJ, Lozano MV, Arroyo-Jimenez MM, Ramos-Membrive R, Peñuelas I, Mabondzo A, Préat V, Teixidó M, Giralt E, Alonso MJ. (2018). PGA enveloped octaarginine-peptide nanocomplexes: An oral peptide delivery strategy. J Control Release. 276:125-139.

f. Niu Z, Tedesco E, Benetti F, Mabondzo A, Montagner IM, Marigo I, Gonzalez-Touceda D, Tovar S, Diéguez C, Santander-Ortega MJ, Alonso MJ. (2017). Rational design of polyarginine nanocapsules intended to help peptides overcoming intestinal barriers. J Control Release. 263:4-17.

g. Tsaioun K, Bottlaender M, Mabondzo A; Alzheimer's Drug Discovery Foundation (2009). ADDME--Avoiding Drug Development Mistakes Early: central nervous system drug discovery perspective. BMC Neurol. 9 Suppl 1: S1. Review.

h. Bousquet L, Pruvost A, Guyot AC, Farinotti R, Mabondzo A (2009). Combination of Tenofovir and Emtricitabine plus Efavirenz: In Vitro Modulation of ABC transporter and Intracellular Drug Accumulation. Antimicrob Agents Chemother. 53(3):896-902.

i. Hembury A, Mabondzo A (2008). Endothelin-1 Reduces P-Glycoprotein Transport Activity in an In Vitro Model of Human Adult Blood-brain Barrier. Cell Mol Cell Mol Neurobiol. 28(7):915-21.

j. Bousquet L, Roucairol C, Hembury A, Nevers MC, Créminon C, Farinotti R, Mabondzo A (2008). Comparison of ABC transporter modulation by atazanavir in lymphocytes and human brain endothelial cells:ABC transporters are involved in the atazanavir-limited passage across an in vitro human model of the blood-brain barrier. AIDS Research and Human retroviruses 24(9):1147-1154.

k. Bousquet L, Pruvost A, Didier N, Farinotti R, Mabondzo A (2008). Inhibitor and Substrate Properties of Emtricitabine in Favor of Interactions with MultiDrug Resistance Associated Proteins. Eur J Pharm Sci. 35(4):247-56.

6- Bio-drugs and diagnostic approaches for brain tumor diseases

a. A Herbet, N Costa, N Leventoux, A Mabondzo, JY Couraud, A Borrull, JP Hugnot, D Boquet.2018 Antibodies targeting human endothelin 1 receptors reveal different conformational states in cancer cells. Physiol. Res. 67, 257–264.

b. Richard, S., Boucher, M., Saric, A., Herbet, A., Lalatonne, Y., X. Petit, P., Mériaux, S., Boquet, D., Motte, L., 2017. Optimization of pegylated iron oxide nanoplatforms for antibody coupling and bio-targeting. J. Mater. Chem. B 5, 2896–2907. doi:10.1039/C6TB03080G

c. N Martin, N Costa, F Wien, FM Winnik, Celine Ortega, Amaury Herbet, Didier Boquet,Christophe Tribet, 2017. Refolding of Aggregation-prone ScFv Antibody Fragments Assisted by Hydrophobically-Modified Poly(sodium acrylate) Derivatives. Macromolecular Bioscience.17.

d. Aurélie Borrull, Bertrand Allard, Anne Wijkhuisen, Amaury Herbet, Patricia Lamourette, Wided Birouk, Denis Leiber, Zahra Tanfin, Frédéric Ducancel, Didier Boquet*, Philippe Robin* and Jean-Yves Couraud 2016 Rendomab B4, a monoclonal antibody that discriminates the human endothelin B receptor of melanoma cells and inhibits their migration. mAbs 8, 1371–1385. doi:10.1080/19420862.2016.1208865.

e. Sophie Richard, Marianne Boucher, Amaury Herbet, Yoann Lalatonne, Sébastien Mériaux, Laurence Motte, Didier Boquet Endothelin B receptors targeted by iron oxide nanoparticles functionalized with a specific antibody: toward immunoimaging of brain tumors. 2015 J Mater Chem B 3, 2939–2942. doi:10.1039/C5TB00103J.

f. Martin, Nicolas; Ma, Dewang; Herbet, Amaury; Boquet, Didier; Winnik, Francoise; Tribet, Christophe Prevention of thermally-induced aggregation of IgG antibodies by non covalent interaction with poly(acrylate) derivatives" Manuscript ID: bm-2014-005756. Biomacromolecules 15, 2952–2962. doi:10.1021/bm5005756.

g. Allard, B., Wijkhuisen, A., Deshayes, F., Borrull, A., Priam, F., Lamourette, P., Ducancel, F., Boquet, D. and Couraud, J.Y. 2013. Generation and characterization of rendomab-B1, a monoclonal antibody displaying potent and specific antagonism of the human endothelin B receptor. Mabs. 5, 1-14. doi: 10.4161/mabs.2269 10.4161/mabs.226966

h. Ortega, C., Herbet, A., Richard, S., Kersual, N., Costa, N., Pèlegrin, A., Ducancel, F., Couraud, J.-Y., Navarro-Teulon, I., Boquet, D., 2013. High level prokaryotic expression of anti-Müllerian inhibiting substance type II receptor diabody, a new recombinant antibody for in vivo ovarian cancer imaging. Journal of Immunological Methods. 387, 11-20. doi: 10.1016/j.jim.2012.08.003

i. Allard, B., Priam, F., Deshayes, F., Ducancel, F., Boquet, D., Wijkhuisen, A., Couraud, J.-Y., 2011. Electroporation-Aided DNA Immunization Generates Polyclonal Antibodies Against the Native Conformation of Human Endothelin B Receptor. DNA and Cell Biology 30, 727–737. doi: 10.1089/dna.2011.1239


a. Dézard S, Taran F, Trotier-Faurion A, Mabondzo A. "Method for preparing creatine fatty esters, creatine fatty esters thus prepared and uses thereof" EP 2 692 719 A1.

b. Mabondzo A, Ullio-Gamboa G, Dézard S, Taran F, Guyot AC, Loreau O, Benech H "Microemulsion containing creatine fatty ester, method for preparing said micro-emulsion and use thereof" PCT/EP2019/061293.

c. Mabondzo A, Ullio-Gamboa G, Dézard S, Taran F, Guyot AC, Benech H, Loreau O, "Protection of formulations/molecules/indications: Microemulsion (with ionic surfactant) containing creatine fatty ester, method for preparing said micro-emulsion and use thereof". EP19305548.0

d. Mabondzo A, Leuxe C, Oumata N, Meijer L. "Purine derivatives for use as medicament and for use in treating neurodegenerative or neuro-inflammatory disorders" PCT/EP2018/059059

e. Mabondzo A, Guyot AC, Costa N, Pruvost A, Galons H, Oumata N, Disdier C, Stonestreet B. "Purine derivatives as drugs for the treatment of neonatal hypoxia-ischemia brain injury and related diseases" Filled in May 2020

f. Mabondzo A, Joudinaud T, Benech H, "Pharmaceutical compositions for treating infection by a neurotropic virus" EP 203805207.8, Filled July 2020.

g. Ducancel, F., Boquet, D., Couraud, J.Y., Wijkhuisen, A.; Allard, B.; Patent WO/2012/045776. Antagonist antibody of endothelin receptor subtype b, and uses thereof.

h. D Boquet, F Ducancel, A Herbet, N Costa, JP Hugnot. Antibodies against the endothelin receptor subtype b, and uses thereof. PCT/EP2017/065442 22 june 2017 WO 2017/220739 A1.

i. D Boquet, A Herbet, F Ducancel, N Costa, JY Couraud, JP Hugnot.  Antibodies against the endothelin receptor subtype a, and uses thereof. French patent 07/02/2018 2018FR-0051026 WO2019/155151.