Safety and Efficacy of Stem Cell Small Extracellular Vesicles in Patients With Retinitis Pigmentosa

Summary

The aim of this clinical trials is to evaluate the safety and efficacy of intravitreal injection of GMP-compliant BM-MSC-derived sEVs in patients with retinitis pigmentosa.

Timeline

Start

2024-05-23

Primary completion

2026-12-31

Completion

2027-12-31

Publications

• Background Cremers FPM, Boon CJF, Bujakowska K, Zeitz C. Special Issue Introduction: Inherited Retinal Disease: Novel Candidate Genes, Genotype-Phenotype Correlations, and Inheritance Models. Genes (Basel). 2018 Apr 16;9(4):215. doi: 10.3390/genes9040215.
• Background Duncan JL, Pierce EA, Laster AM, Daiger SP, Birch DG, Ash JD, Iannaccone A, Flannery JG, Sahel JA, Zack DJ, Zarbin MA; and the Foundation Fighting Blindness Scientific Advisory Board. Inherited Retinal Degenerations: Current Landscape and Knowledge Gaps. Transl Vis Sci Technol. 2018 Jul 18;7(4):6. doi: 10.1167/tvst.7.4.6. eCollection 2018 Jul. No abstract available.
• Background Rodrigues GA, Shalaev E, Karami TK, Cunningham J, Slater NKH, Rivers HM. Pharmaceutical Development of AAV-Based Gene Therapy Products for the Eye. Pharm Res. 2018 Dec 27;36(2):29. doi: 10.1007/s11095-018-2554-7.
• Background Lipinski DM, Thake M, MacLaren RE. Clinical applications of retinal gene therapy. Prog Retin Eye Res. 2013 Jan;32:22-47. doi: 10.1016/j.preteyeres.2012.09.001. Epub 2012 Sep 17.
• Background Verbakel SK, van Huet RAC, Boon CJF, den Hollander AI, Collin RWJ, Klaver CCW, Hoyng CB, Roepman R, Klevering BJ. Non-syndromic retinitis pigmentosa. Prog Retin Eye Res. 2018 Sep;66:157-186. doi: 10.1016/j.preteyeres.2018.03.005. Epub 2018 Mar 27.
• Background Nauta AJ, Fibbe WE. Immunomodulatory properties of mesenchymal stromal cells. Blood. 2007 Nov 15;110(10):3499-506. doi: 10.1182/blood-2007-02-069716. Epub 2007 Jul 30.
• Background Salehi H, Amirpour N, Razavi S, Esfandiari E, Zavar R. Overview of retinal differentiation potential of mesenchymal stem cells: A promising approach for retinal cell therapy. Ann Anat. 2017 Mar;210:52-63. doi: 10.1016/j.aanat.2016.11.010. Epub 2016 Dec 13.
• Background Holan V, Hermankova B, Krulova M, Zajicova A. Cytokine interplay among the diseased retina, inflammatory cells and mesenchymal stem cells - a clue to stem cell-based therapy. World J Stem Cells. 2019 Nov 26;11(11):957-967. doi: 10.4252/wjsc.v11.i11.957.
• Background Tuekprakhon A, Sangkitporn S, Trinavarat A, Pawestri AR, Vamvanij V, Ruangchainikom M, Luksanapruksa P, Pongpaksupasin P, Khorchai A, Dambua A, Boonchu P, Yodtup C, Uiprasertkul M, Sangkitporn S, Atchaneeyasakul LO. Intravitreal autologous mesenchymal stem cell transplantation: a non-randomized phase I clinical trial in patients with retinitis pigmentosa. Stem Cell Res Ther. 2021 Jan 9;12(1):52. doi: 10.1186/s13287-020-02122-7.
• Background He L, Chen Y, Ke Z, Pang M, Yang B, Feng F, Wu Z, Liu C, Liu B, Zheng X, Wu T, Shu T. Exosomes derived from miRNA-210 overexpressing bone marrow mesenchymal stem cells protect lipopolysaccharide induced chondrocytes injury via the NF-kappaB pathway. Gene. 2020 Aug 15;751:144764. doi: 10.1016/j.gene.2020.144764. Epub 2020 May 16.
• Background Keshtkar S, Azarpira N, Ghahremani MH. Mesenchymal stem cell-derived extracellular vesicles: novel frontiers in regenerative medicine. Stem Cell Res Ther. 2018 Mar 9;9(1):63. doi: 10.1186/s13287-018-0791-7.
• Background Vilaca-Faria H, Salgado AJ, Teixeira FG. Mesenchymal Stem Cells-derived Exosomes: A New Possible Therapeutic Strategy for Parkinson's Disease? Cells. 2019 Feb 2;8(2):118. doi: 10.3390/cells8020118.
• Background Zhao T, Sun F, Liu J, Ding T, She J, Mao F, Xu W, Qian H, Yan Y. Emerging Role of Mesenchymal Stem Cell-derived Exosomes in Regenerative Medicine. Curr Stem Cell Res Ther. 2019;14(6):482-494. doi: 10.2174/1574888X14666190228103230.
• Background Frydrychowicz M, Kolecka-Bednarczyk A, Madejczyk M, Yasar S, Dworacki G. Exosomes - structure, biogenesis and biological role in non-small-cell lung cancer. Scand J Immunol. 2015 Jan;81(1):2-10. doi: 10.1111/sji.12247.
• Background Mead B, Ahmed Z, Tomarev S. Mesenchymal Stem Cell-Derived Small Extracellular Vesicles Promote Neuroprotection in a Genetic DBA/2J Mouse Model of Glaucoma. Invest Ophthalmol Vis Sci. 2018 Nov 1;59(13):5473-5480. doi: 10.1167/iovs.18-25310.
• Background Safwat A, Sabry D, Ragiae A, Amer E, Mahmoud RH, Shamardan RM. Adipose mesenchymal stem cells-derived exosomes attenuate retina degeneration of streptozotocin-induced diabetes in rabbits. J Circ Biomark. 2018 Oct 28;7:1849454418807827. doi: 10.1177/1849454418807827. eCollection 2018 Jan-Dec.
• Background Zhang W, Wang Y, Kong Y. Exosomes Derived From Mesenchymal Stem Cells Modulate miR-126 to Ameliorate Hyperglycemia-Induced Retinal Inflammation Via Targeting HMGB1. Invest Ophthalmol Vis Sci. 2019 Jan 2;60(1):294-303. doi: 10.1167/iovs.18-25617.
• Background Ma M, Li B, Zhang M, Zhou L, Yang F, Ma F, Shao H, Li Q, Li X, Zhang X. Therapeutic effects of mesenchymal stem cell-derived exosomes on retinal detachment. Exp Eye Res. 2020 Feb;191:107899. doi: 10.1016/j.exer.2019.107899. Epub 2019 Dec 19.
• Background Moisseiev E, Anderson JD, Oltjen S, Goswami M, Zawadzki RJ, Nolta JA, Park SS. Protective Effect of Intravitreal Administration of Exosomes Derived from Mesenchymal Stem Cells on Retinal Ischemia. Curr Eye Res. 2017 Oct;42(10):1358-1367. doi: 10.1080/02713683.2017.1319491. Epub 2017 Jun 21.
• Background Elbay A, Ercan C, Akbas F, Bulut H, Ozdemir H. Three new circulating microRNAs may be associated with wet age-related macular degeneration. Scand J Clin Lab Invest. 2019 Oct;79(6):388-394. doi: 10.1080/00365513.2019.1637931. Epub 2019 Jul 5.
• Background Bai L, Shao H, Wang H, Zhang Z, Su C, Dong L, Yu B, Chen X, Li X, Zhang X. Effects of Mesenchymal Stem Cell-Derived Exosomes on Experimental Autoimmune Uveitis. Sci Rep. 2017 Jun 28;7(1):4323. doi: 10.1038/s41598-017-04559-y.
• Background Durani P, Leaper D. Povidone-iodine: use in hand disinfection, skin preparation and antiseptic irrigation. Int Wound J. 2008 Jun;5(3):376-87. doi: 10.1111/j.1742-481X.2007.00405.x.

Drugs

Indications