Project Implementation

On this page, you will find a guide to immerse yourself in our project implementation, as well as the conclusions and references.

Translating our project into a real-world application

The figure above is an overview of the lifecycle of an ATMP (key steps of the drug pharmaceutical development). Source: https://doi.org/10.1016/j.jcyt.2023.12.005

Reneurish is still in the early stages of development, and a long journey lies ahead before it can become a viable treatment for stroke patients. Our Implementation page outlines a clear roadmap from where we are today to our envisioned future, detailing the steps necessary to bring our therapy to market. Developing and gaining approval for Advanced Therapy Medicinal Products is a complex, multiphase process, often requiring significant resources and time. In light of this, we have created a comprehensive action plan designed to maximize our chances of success.

Conclusion

The successful integration of Reneurish into real-world applications depends on several key factors. Understanding our end-users and stakeholders is essential, as they will be the primary beneficiaries. Identifying the problem we aim to solve is foundational for our product design, informed by expert interviews and extensive literature research that define the desirable properties of our therapy.

Our implementation plan emphasizes patient safety and a commitment to transforming lives while addressing potential challenges. Through this thorough approach, we aim to protect the integrity of our therapy and enhance health outcomes, ultimately providing a sustainable solution that improves the quality of life for patients.

References

[1] - WHO EMRO - Stroke, Cerebrovascular accident. (2024). Who.int
[2] - Pu, L., Wang, L., Zhang, R., Zhao, T., Jiang, Y., & Han, L. (2023). Projected Global Trends in Ischemic Stroke Incidence, Deaths and Disability-Adjusted Life Years From 2020 to 2030. Stroke, 54(5), 1330–1339. https://doi.org/10.1161/strokeaha.122.040073
[3] - Gutierrez-Aranda, I., Ramos-Mejia, V., Bueno, C., Munoz-Lopez, M., Real, P. J., Mácia, A., Sanchez, L., Ligero, G., Garcia-Parez, J. L., & Menendez, P. (2010). Human Induced Pluripotent Stem Cells Develop Teratoma More Efficiently and Faster Than Human Embryonic Stem Cells Regardless the Site of Injection. Stem Cells, 28(9), 1568–1570. https://doi.org/10.1002/stem.471
[4] - Li, X., Huang, M., Zhao, R., Zhao, C., Liu, Y., Zou, H., Chen, L., Guan, Y., & Y. Alex Zhang. (2018). Intravenously Delivered Allogeneic Mesenchymal Stem Cells Bidirectionally Regulate Inflammation and Induce Neurotrophic Effects in Distal Middle Cerebral Artery Occlusion Rats Within the First 7 Days After Stroke. Cellular Physiology and Biochemistry, 46(5), 1951–1970. https://doi.org/10.1159/000489384
[5] - Wang, C., Zhang, Y., Ding, J., Zhao, Z., Qian, C., Luan, Y., & Teng, G.-J. (2017). Nicotinamide Administration Improves Remyelination after Stroke. Neural Plasticity, 2017, 1–12. https://doi.org/10.1155/2017/7019803
[6] - Allen, S. J., Watson, J. J., Shoemark, D. K., Barua, N. U., & Patel, N. K. (2013). GDNF, NGF and BDNF as therapeutic options for neurodegeneration. Pharmacology & Therapeutics, 138(2), 155–175. https://doi.org/10.1016/j.pharmthera.2013.01.004
[7] - Wolf-Rüdiger Schäbitz, Steigleder, T., Cooper-Kuhn, C. M., Schwab, S., Sommer, C., Schneider, A., & H. Georg Kuhn. (2007). Intravenous Brain-Derived Neurotrophic Factor Enhances Poststroke Sensorimotor Recovery and Stimulates Neurogenesis. Stroke, 38(7), 2165–2172. https://doi.org/10.1161/strokeaha.106.477331
[8] - Burdick, J., Mauck, R., & Gerecht, S. (2016). To Serve and Protect: Hydrogels to Improve Stem Cell-Based Therapies. Cell Stem Cell, 18(1), 13–15. https://doi.org/10.1016/j.stem.2015.12.004
[9] - Nayeon, C. (2016). Therapeutic Effect of BDNF-Overexpressing Human Neural Stem Cells (HB1.F3.BDNF) in a Rodent Model of Middle Cerebral Artery Occlusion - Da-Jeong Chang, Nayeon Lee, Chunggab Choi, Iksoo Jeon, Seung-Hun Oh, Dong Ah Shin, Tae-Sun Hwang, Hong J. Lee, Seung U. Kim, Hyeyoung Moon, Kwan Soo Hong, Kyung-Sun Kang, Jihwan Song, 2013. Cell Transplantation. https://journals.sagepub.com/doi/full/10.3727/096368912X657323
[10] - Muir, K. W., Bulters, D., Willmot, M., Sprigg, N., Dixit, A., Ward, N., Tyrrell, P., Majid, A., Dunn, L., Bath, P., Howell, J., Stroemer, P., Pollock, K., & Sinden, J. (2020). Intracerebral implantation of human neural stem cells and motor recovery after stroke: multicentre prospective single-arm study (PISCES-2). Journal of Neurology, Neurosurgery & Psychiatry, 91(4), 396–401. https://doi.org/10.1136/jnnp-2019-322515
[11] - Noh, J.-E., Oh, S.-H., Park, I.-H., & Song, J. (2020). Intracerebral Transplants of GMP-Grade Human Umbilical Cord-Derived Mesenchymal Stromal Cells Effectively Treat Subacute-Phase Ischemic Stroke in a Rodent Model. Frontiers in Cellular Neuroscience, 14. https://doi.org/10.3389/fncel.2020.546659
[12] - Kawabori, M., Kuroda, S., Shichinohe, H., Kahata, K., Shiratori, S., Ikeda, S., Harada, T., Hirata, K., Tha, K. K., Aragaki, M., Terasaka, S., Ito, Y. M., Nishimoto, N., Ohnishi, S., Yabe, I., Kudo, K., Houkin, K., & Fujimura, M. (2024). Intracerebral transplantation of MRI-trackable autologous bone marrow stromal cells for patients with subacute ischemic stroke. Med, 5(5), 432-444.e4. https://doi.org/10.1016/j.medj.2024.02.009
[13] - Zhang, G., Li, Y., Reuss, J. L., Liu, N., Wu, C., Li, J., Xu, S., Wang, F., Hazel, T. G., Cunningham, M., Zhang, H., Dai, Y., Hong, P., Zhang, P., He, J., Feng, H., Lu, X., Ulmer, J. L., Johe, K. K., & Xu, R. (2019). Stable Intracerebral Transplantation of Neural Stem Cells for the Treatment of Paralysis Due to Ischemic Stroke. Stem Cells Translational Medicine, 8(10), 999–1007. https://doi.org/10.1002/sctm.18-0220
[14] - Noh, J.-E., Oh, S.-H., Park, I.-H., & Song, J. (2020). Intracerebral Transplants of GMP-Grade Human Umbilical Cord-Derived Mesenchymal Stromal Cells Effectively Treat Subacute-Phase Ischemic Stroke in a Rodent Model. Frontiers in Cellular Neuroscience, 14. https://doi.org/10.3389/fncel.2020.546659
[15] - Singh, M., Pandey, P. K., Bhasin, A., Padma, M. V., & Mohanty, S. (2020). Application of Stem Cells in Stroke: A Multifactorial Approach. Frontiers in Neuroscience, 14. https://doi.org/10.3389/fnins.2020.00473
[16] - Gao, X., Liu, D., Yue, K., Zhang, Z., Jiang, X., & Luo, P. (2024). Revolutionizing Ischemic Stroke Diagnosis and Treatment: The Promising Role of Neurovascular Unit-Derived Extracellular Vesicles. Biomolecules, 14(3), 378–378. https://doi.org/10.3390/biom14030378
[17] - Chiang, T., Messing, R. O., & Chou, W.-H. (2011). Mouse Model of Middle Cerebral Artery Occlusion. Journal of Visualized Experiments, 48. https://doi.org/10.3791/2761
[18] - Crupi, R., Rosanna Di Paola, Esposito, E., & Cuzzocrea, S. (2017). Middle Cerebral Artery Occlusion by an Intraluminal Suture Method. Methods in Molecular Biology, 393–401. https://doi.org/10.1007/978-1-4939-7571-6_31
[19] - Loriana Vitillo, Durance, C., Hewitt, Z., Moore, H., Smith, A., & Vallier, L. (2020). GMP-grade neural progenitor derivation and differentiation from clinical-grade human embryonic stem cells. Stem Cell Research & Therapy, 11(1). https://doi.org/10.1186/s13287-020-01915-0
[20] - Quantum: Automated Cell Culture. (2018). Terumobct.com
[21] - Revathiswari Tirughana, Metz, M. Z., Li, Z., Hall, C., Hsu, D., Beltzer, J., Annala, A. J., Oganesyan, D., Gutova, M., & Aboody, K. S. (2018). GMP Production and Scale-Up of Adherent Neural Stem Cells with a Quantum Cell Expansion System. Molecular Therapy — Methods & Clinical Development, 10, 48–56. https://doi.org/10.1016/j.omtm.2018.05.006
[22] - Europe PMC. (2016). Europe PMC.