Research Information System
ÖZ U. C. (Executive), KÜÇÜKTÜRKMEN B., KURTER S., BOZKIR A., ESENDAĞLI G., ACAR ÖZEN N. P., et al.
2025 - 2027
Multiple sclerosis (MS) is a chronic autoimmune disease characterized by inflammation, demyelination, and axonal degeneration, affecting the central nervous system. According to the International Multiple Sclerosis Federation’s 2021 data, there are an estimated 2.8 million MS patients worldwide. Although progress has been made with treatments developed for various types of MS, there remains a significant unmet need for highly effective therapies that also promote myelin production in progressive MS. Miyelin oligodendrosit glikoprotein (MOG) is a molecule expressed on the outer surface of myelin in the central nervous system. Due to the detection of an excess of T cells reactive to MOG in MS patients, it has emerged as an important target antigen in MS and related animal modelsCopanlisib (CPS) is an FDA-approved potent phosphatidylinositol 3-kinase (PI3K) inhibitör. In the context of this project proposal, it is aimed to develop hydrogel and nanoparticle-based formulations to induce immune tolerance against MOG, which will contain the MOG peptide as an immune tolerant agent and the CPS molecule as an immunomodulator in cases where the immune system is overactive (such as MS). The goal is twofold: first, to present the MOG peptide to the immune system in a controlled manner, allowing it to recognize MOG as a component of the organism rather than a foreign aggressor, thereby reducing the autoimmune response; second, to utilize CPS for overall immune modulation, creating a high-efficacy MS treatment through a combined approach strategy. This represents the world’s first potential combination of an autoantigen with a phosphatidylinositol 3-kinase inhibitor for MS. With the proposed project, for the first time in the literature, temperature responsive hydrogel systems based on modified PEG-PCL-PEG polymer will be developed to provide effective control over the release of MOG peptide. Additionally, within the scope of this project proposal, a series of novel modifications (Chlorine, Amine, Carboxylic acid, Hydroxyl, Phosphate, and Mannose) will be made to the PEG-PCL-PEG polymer chain, potentially pioneering other applications for this material. Furthermore, the CPS molecule will be encapsulated primarily within nanoparticles and subsequently formulated within the hydrogel system developed as part of the project. With the proposed project, the following studies, planned to be introduced to the world literature for the first time, can be listed as follows: 1) For the first time, the combined potential use of an autoantigen with a phosphatidylinositol 3-kinase inhibitor against MS will be demonstrated. 2) Modified PEG-PCL-PEG temperature-sensitive hydrogel systems will be developed to effectively control the release of MOG peptide. 3) The novel modification of the PEG-PCL-PEG polymer chain within this project proposal may pave the way for its use in treating different diseases. 4) Nanoparticle systems loaded with Copanlisib will be developed for the first time. In conclusion, the multidisciplinary research team comprising applied, fundamental, and clinical sciences, brought together by this project proposal, will integrate formulation development for MS and clinical perspectives. As a result, the planned studies within the scope of the project will be completed in line with the intended objectives.