InflammX Therapeutics, Inc.
Key Publications - Connexin hemichannel modualtion, Inflammasome, Ocular
(note: Tonabersat = Xiflam)
1. Mat Nor MN, Rupenthal ID, Green CR, Acosta ML. Differential action of connexin hemichannel and pannexin channel therapeutics for potential treatment of retinal diseases. Int. J. Mol. Sci. Special Edition: Therapeutic Potential of Targeting Connexins in Managing Disease Onset and Progression. Int. J. Mol. Sci. 2021, 22, 1755.
2. Lyon H, Shome A, Rupenthal ID, Green CR, Mugisho OO. Tonabersat Inhibits Connexin43 Hemichannel Opening and Inflammasome Activation in an In Vitro Retinal Epithelial Cell Model of Diabetic Retinopathy. Int. J. Mol. Sci. 2021, 22, 298.
3. Louie HH, Shome A, Rupenthal ID, Green CR, Mugisho OO. Connexin43 hemichannel block inhibits NLRP3 inflammasome activation in a human retinal explant model of diabetic retinopathy. Experimental Eye Research. 2020; 202:108384. PMID: 33285185.
4. Coutinho FP, Green CR, Acosta ML, Rupenthal ID. Xentry-Gap19 inhibits Connexin43 hemichannel opening especially during hypoxic injury. Drug Delivery and Translational Research. 2020; 10:751–765.
5. Mugisho OO, Rupenthal ID, Paquet-Durand F, Acosta ML, Green CR. Targeting connexin hemichannels to control the inflammasome: the correlation between connexin43 and NLRP3 expression in chronic eye disease. Expert Opinion on Therapeutic Targets. 2019. 23:855-863.
6. Mat Nor MN, Rupenthal ID, Green CR, Acosta ML. Connexin hemichannel block using orally delivered tonabersat improves outcomes in animal models of retinal disease. Neurotherapeutics. 2020; 17:371-387.
7. Kuo C, Green CR, Rupenthal ID, Mugisho OO. Connexin43 hemichannel block protects against retinal pigment epithelial cell barrier breakdown. Acta Diabetol. 2019 Apr 27. doi: 10.1007/s00592-019-01352-3. [Epub ahead of print]
8. Mugisho OO, Green CR, Zhang J, Acosta ML, Rupenthal ID. Connexin43 hemichannels: a potential drug target for the treatment of diabetic retinopathy. Drug Discov Today. 2019; 24:1627-1636. Review.
9. Mugisho OO, Green CR, Squirrell DM, Bould S, Danesh-Meyer HV, Zhang J, Acosta ML, Rupenthal ID. Connexin43 hemichannel block protects against the development of diabetic retinopathy signs in a mouse model of the disease. Journal of Molecular Medicine (Berl). 2019; 97:215-229.
10. Mat Nor MN, Guo CX, Rupenthal ID, Chen YS, Green CR, Acosta ML. Sustained Connexin43 Mimetic Peptide Release From Loaded Nanoparticles Reduces Retinal and Choroidal Photodamage. Investigative Ophthalmology and Visual Science. 2018; 59: 3682-3693.
11. Huang D, Chen YS, Green CR, Rupenthal ID. Hyaluronic acid coated albumin nanoparticles for targeted peptide delivery in the treatment of retinal ischaemia. Biomaterials. 2018; 168:10-23.
12. Galinsky R, Davidson JO, Dean JM, Green CR, Bennet L, Gunn AJ. Glia and hemichannels: Key mediators of perinatal encephalopathy. Neural Regeneration Research. 2018; 13:181-189.
13. Ziaei M, Greene C, Green CR. Wound healing in the eye: Therapeutic prospects. Adv Drug Deliv Rev. 2018; 126: 162-176.
14. Mugisho OO, Green CR, Kho DT, Zhang J, Scott Graham E, Acosta ML, Rupenthal ID. The inflammasome pathway is amplified and perpetuated in an autocrine manner through connexin43 hemichannel mediated ATP release. Biochim Biophys Acta. 2018; 1862:385-393.
15. Tonkin RS, Bowles C, Perera CJ, Keating BA, Makker PGS, Duffy SS, Lees JG, Tran C, Don AS, Fath T, Liu L, O'Carroll SJ, Nicholson LFB, Green CR, Gorrie C, Moalem-Taylor G. Attenuation of mechanical pain hypersensitivity by treatment withPeptide5, a connexin-43 mimetic peptide, involves inhibition of NLRP3 inflammasome in nerve-injured mice. Experimental Neurology 2018; 300: 1–12.
16. Mugisho OO, Green CR, Zhang J, Binz N, Acosta ML, Rakoczy E, Rupenthal ID. Immunohistochemical Characterization of Connexin43 Expression in a Mouse Model of Diabetic Retinopathy and in Human Donor Retinas. Int J Mol Sci. 2017 Nov 29;18(12). pii: E2567. doi: 10.3390/ijms18122567.
17. Leybaert L, Lampe PD, Dhein S, Kwak BR, Ferdinandy P, Beyer EC, Laird DW, Naus CC, Green CR, Schulz R. Connexins in cardiovascular health and disease: pharmacological implications. Pharmacological Reviews. 2017; 69:396-478. Invited Review.
18. Kim Y, Griffin JM, Mohd N Mat Nor, Zhang J, Freestone PS, Danesh-Meyer HV, Rupenthal ID, Acosta ML, Nicholson LFB, O’Carroll SJ, Green. CR. Tonabersat prevents inflammatory damage in the central nervous system by blocking Connexin43 hemichannels. Neurotherapeutics, 2017; doi: 10.1007/s13311-017-0536-9.
19. Mao Y, Nguyen T, Tonkin RS, Lees JG, Warren C, O’Carroll SJ, Nicholson LFB, Green CR, Moalem-Taylor G, Gorrie CA. Characterisation of Peptide5 Systemic Administration for Treating Traumatic Spinal Cord Injured Rats. Experimental Brain Research. Exp Brain Res. 2017; 235:3033-3048.
20. Galinsky R, Davidson JO, Lear CA, Bennet L, Green CR, Gunn AJ.Connexin hemichannel blockade improves survival of striatal GABA-ergic neurons after global cerebral ischaemia in term-equivalent fetal sheep. Scientific Reports. 2017; DOI:10.1038/s41598-017-06683-1.
21. Kim Y, Davidson JO, Green CR, Nicholson LF, O'Carroll SJ, Zhang J. Connexins and Pannexins in cerebral ischemia. Biochim Biophys Acta. 2017 Mar 25. pii: S0005-2736(17)30100-1. doi: 10.1016/j.bbamem.2017.03.018. Review.
22. Kim Y, Griffin JM, Harris PWR, Chan SHC, Nicholson LFB, Brimble MA, O’Carroll SJ, Green CR. Characterizing the mode of action of extracellular Connexin43 channel blocking mimetic peptides in an in vitro ischemia injury model. Biochim Biophys Acta. 2017; 1861:68-78.
23. Mao Y, Tonkin RS, Nguyen T, O’Carroll SJ, Nicholson LFB, Green CR, Moalem-Taylor G, Gorrie CA. Systemic administration of Connexin43 mimetic peptide improves functional recovery following traumatic spinal cord injury in adult rats. J Neurotrauma. 2016; 33:1-13.
24. Guo CX, Nor MNM, Danesh-Meyer HV, Vessey K, Fletcher EL, O’Carroll SJ, Acosta ML, Green CR. Connexin43 mimetic peptide improves retinal function and reduces inflammation in a light damaged albino rat model. Investigative Ophthalmology and Visual Science, 2016; 57: 3961-3973.
25. Kim Y, Davidson JO, Gunn KC, Phillips AR, Green CR, Gunn AJ. Role of hemichannels in CNS inflammation and the inflammasome pathway. Adv Protein Chem Struct Biol. 2016; 104:1-37. Review.
26. Willebrords J, Crespo Yanguas S, Maes M, Decrock E, Wang N, Leybaert L, Kwak BR, Green CR, Cogliati B, Vinken M. Connexins and their channels in inflammation. Crit Rev Biochem Mol Biol. 2016; 7:1-27. Review.
27. Danesh-Meyer HV, Zhang J, Acosta ML, Rupenthal ID, Green CR. Connexin43 in retinal injury and disease. Prog Retin Eye Res. 2015; 51:41-68. Review.
28. Chen Y-S, Green CR, Wang K, Danesh-Meyer HV, Rupenthal ID. Sustained intravitreal delivery of connexin43 mimetic peptide by poly(D,L-lactide-co-glycolide) acid micro- and nanoparticles - Closing the gap in retinal ischaemia. European Journal of Pharmaceutics and Biopharmaceutics. 2015. 95(Pt B):378-386.
29. Becker DL, Phillips AR, Duft BJ, Kim Y, Green CR. Translating connexin biology into therapeutics. Semin Cell Devel Biol. 2015; 50:49-58. Review.
30. Chen Y-S, Green CR, Teague R, Perrett J, Danesh-Meyer HV, Toth I, Rupenthal ID. Intravitreal injection of lipoamino acid modified Connexin43 mimetic peptide enhances neuroprotection after retinal ischemia. Drug Deliv Transl Res. 2015; 5:480-488.
31. Decrock E, De Bock M, Wang N, Bultynck G, Giaume C, Naus CC, Green CR, Leybaert L. Connexin and pannexin signaling pathways, an architectural blueprint for CNS physiology and pathology? Cell Mol Life Sci. 2015; 72:2823-2851. Review.
32. Chen, Y-S, Green CR, Danesh-Meyer HV, Rupenthal ID. Neuroprotection in the treatment of glaucoma – A focus on connexin43 gap junction channel blockers. Eur J Pharm Biopharm. 2015; 95(Pt B):182-193. Review.
33. Davidson JO, Drury PP, Green CR, Nicholson LF, Bennet L, Gunn AJ. Connexin hemichannel blockade is neuroprotective after asphyxia in preterm fetal sheep. PLoS One. 2014; 9(5):e96558.
34. Guo CX, Tan H, Green CR, Danesh-Meyer HV, Acosta ML. Gap junction proteins in the light-damaged albino rat model. Molecular Vision. 2014;20:670-682.
35. O’Caroll SJ, Gorrie CA, Velamoor S, Green CR, Nicholson LF. Connexin43 mimetic peptide is neuroprotective and improves function following spinal cord injury. Neuroscience Research. 2013; 75: 256-267.
36. Davidson JO, Green CR, Bennet L, Nicholson LFB, Danesh-Meyer H, O’Carroll SJ. Gunn AJ. A key role for connexin hemichannels in spreading ischemic brain injury. Current Drug Targets. 2013; 14:36 - 46. Review.
37. Ormonde S, Chou C, Goold L, Petsoglou C, Al-Taie R, Sherwin T, McGhee CNJ, Green CR. Regulation of connexin43 gap junction protein triggers vascular recovery and healing in human ocular persistent epithelial defect wounds. Journal of Membrane Biology. 2012; 245:381-388.
38. Deva NC, Zhang J, Green CR, Danesh-Meyer HV. Connexin43 modulation inhibits scarring in a rabbit eye glaucoma trabeculectomy Model. Inflammation. 2012; 35:1276-1286.
39. Kerr NM, Johnson CS, Zhang J, Eady EK, Green CR, Danesh-Meyer HV. High pressure-induced retinal ischemia reperfusion causes upregulation of gap junction protein connexin43 prior to retinal ganglion cell loss. Experimental Neurology. 2012; 234:144-152.
40. Grupcheva CN, Laux WT, Rupenthal ID, McGhee J, McGhee CNJ, Green CR. Improved corneal wound healing through modulation of gap junction communication using Connexin43-specific antisense oligodeoxynucleotides. Investigative Ophthalmology and Visual Science. 2012; 53:1130-1138.
41. Danesh-Meyer HV, Kerr NM, Zhang J, Eady EK, O’Carroll SJ, Nicholson LFB, Johnson CS, Green CR. Connexin43 mimetic peptide reduces vascular leak and retinal ganglion cell death following retinal ischaemia. Brain. 2012; 135:506-520.
42. Davidson JO, Green CR, Nicholson LFB, O'Carroll SJ, Fraser M, Bennet L, Gunn AJ. Connexin hemichannel blockade improves outcomes in a model of fetal ischemia. Annals of Neurology. 2012; 71:121-132.
43. Chew SSL, Johnson CS, Green CR, Danesh-Meyer HV. Response of retinal Connexin43 to optic nerve injury. Investigative Ophthalmology and Visual Science. 2012; 52:3620-3629.
44. Kerr NM, Johnson CS, Green CR, Danesh-Meyer HV. Gap junction protein connexin43 (GJA1) in the human glaucomatous optic nerve head and retina. Journal of Clinical Neuroscience. 2011; 18:102-108.
45. Kerr NM, Johnson CS, De Souza CF, Chee KS, Good WR, Green CR, Danesh-Meyer HV. Immunolocalization of Gap Junction Protein Connexin43 (GJA1) in the Human Retina and Optic Nerve. Investigative Opthalmology and Visual Science. 2010; 51:4028-4034.
46. O’Carroll SJ, Alkadhi M, Nicholson LFB, Green CR. A Cx43 mimetic peptide reduces swelling, astrogliosis and neuronal cell death after spinal cord injury. Cell Communication and Adhesion. 2008; 15:27 - 42.
47. Danesh-Meyer HV, Huang R, Nicholson LFB, Green CR. Connexin 43 Antisense Oligonucleotide Treatment Down Regulates the Inflammatory Response in an In Vitro Interphase Organotypic Model of Optic Nerve Ischemia. Journal of Clinical Neuroscience. 2008; 15:1253-1263.
48. Cronin M, Anderson PN, Cook JE, Green CR, Becker DL. Blocking connexin43 expression reduces inflammation and improves functional recovery after spinal cord injury. Mol. Cell. Neurosci. 2008; 39:152-160.
49. Law L-Y, Zhang WV, Stott NS, Becker DL, Green CR. In vitro optimization of antisense oligodexoynucleotide design: An example using the connexin gene family. Journal of Biomolecular Techniques 2006; 17:270 – 282.
50. Cronin M, Anderson PN, Green CR, Becker DL. Antisense delivery and protein knockdown within the intact central nervous system. Frontiers in Bioscience 2006; 11:2967-2975.
51. Coutinho P, Qiu C, Frank S, Wang CM, Brown T, Green CR, Becker DL. Limiting burn extension by transient inhibition of Connexin43 expression at the site of injury. Brit. J. Plast. Surg. 2005; 58:658-667.
52. Qiu C, Coutinho P, Frank S, Franke S, Law L-Y, Martin P, Green CR, Becker DL. Targeting Connexin43 Expression Accelerates the Rate of Wound Repair. Current Biology. 2003; 13:1967-1703.
Key Publications (publications supporting hemichannel modulation of the inflammasome pathway and/or inflammatory cytokine release for non-ocular indications)
1. CHRONIC KIDNEY DISEASE - Price GW, Chadjichristos CE, Kavvadas P, Tang SCW, Yiu WH, Green CR, Potter JA, Siamantouras E, Squires PE, Hills CE. Blocking Connexin-43 mediated hemichannel activity protects against early tubular injury in experimental chronic kidney disease. Cell Commun Signal. 2020;18(1):79. doi: 10.1186/s12964-020-00558.
2. FETAL ISCHEMIA – Yang P, Davidson JO, Fowke TM, Galinsky R, Wassink G, Karunasinghe RN, Prasad JD, Ranasinghe S, Green CR, Bennet L, Gunn AJ, Dean JM. Connexin Hemichannel Mimetic Peptide Attenuates Cortical Interneuron Loss and Perineuronal Net Disruption Following Cerebral Ischemia in Near-Term Fetal Sheep. Int J Mol Sci. 2020; 21:E6475. doi: 10.3390/ijms21186475.
3. Davidson, J.O., Green, C.R., Nicholson, L.F., O'carroll, S.J., Fraser, M., Bennet, L., and Gunn, A.J. (2012). Connexin hemichannel blockade improves outcomes in a model of fetal ischemia. Ann. Neurol. 71, 121-132.
4. Zhou KQ, Green CR, Bennet L, Gunn AJ, Davidson JO. The role of connexin and pannexin channels in perinatal brain injury and inflammation. Frontiers in Physiology. 2019: 27;10:141. Review.
5. FETAL ASPHYXIA - Davidson, J.O., Drury, P.P., Green, C.R., Nicholson, L.F., Bennet, L., and Gunn, A.J. (2014). Connexin hemichannel blockade is neuroprotective after asphyxia in preterm fetal sheep. PLoS ONE 9, e96558.
6. CHRONIC PAIN - Tonkin, R.S., Bowles, C., Perera, C.J., Keating, B.A., Makker, P.G.S., Duffy, S.S., Lees, J.G., Tran, C., Don, A.S., Fath, T., Liu, L., O'carroll, S.J., Nicholson, L.F.B., Green, C.R., Gorrie, C., and Moalem-Taylor, G. (2018). Attenuation of mechanical pain hypersensitivity by treatment with Peptide5, a connexin-43 mimetic peptide, involves inhibition of NLRP3 inflammasome in nerve-injured mice. Exp. Neurol. 300, 1-12.
7. CNS TRAUMA (SPINAL CORD INJURY) - Mao, Y., Nguyen, T., Tonkin, R.S., Lees, J.G., Warren, C., O'carroll, S.J., Nicholson, L.F.B., Green, C.R., Moalem-Taylor, G., and Gorrie, C.A. (2017). Characterisation of Peptide5 systemic administration for treating traumatic spinal cord injured rats. Exp. Brain Res.2017; 235: 3033-3048.
8. Mao Y, Tonkin RS, Nguyen T, O’Carroll SJ, Nicholson LFB, Green CR, Moalem-Taylor G, Gorrie CA. Systemic administration of Connexin43 mimetic peptide improves functional recovery following traumatic spinal cord injury in adult rats. J Neurotrauma. 2016; 33:1-13.
9. O’Carroll SJ, Gorrie CA, Velamoor S, Green CR and Nicholson LFB. Connexin43 mimetic peptide is neuroprotective and improves function following spinal cord injury. Neuroscience Research. 2013; 75:256 - 267.
10. RADIATION NECROSIS. Feldman LA, Haldankar S, O’Carroll SJ, Liu K, Fackelmeier B, Broaddus WC, Anene-maidoh T, Green CR, Garbow JR, Guan J. Connexin43 Expression and Associated Chronic Inflammation Presages the Development of Cerebral Radiation Necrosis. Journal of Neuropathology and Experimental Neurology. 2020; 79: 791–799.
11. SKIN WOUNDS - Coutinho P, Qiu C, Frank S, Wang CM, Brown T, Green CR, Becker DL. Limiting burn extension by transient inhibition of Connexin43 expression at the site of injury. Brit. J. Plast. Surg. 2005; 58:658-667.
12. Qiu C, Coutinho P, Frank S, Franke S, Law L-Y, Martin P, Green CR, Becker DL. Targeting Connexin43 Expression Accelerates the Rate of Wound Repair. Current Biology. 2003; 13:1967-1703.