Akademik Veri Yönetim Sistemi
TÜBİTAK Projesi, 1001 - Bilimsel ve Teknolojik Araştırma Projelerini Destekleme Programı, 2017 - 2021
Multiple sclerosis (MS) is triggered by environmental factors in genetically susceptible individuals and has complex characteristics including demyelination and inflammation of the central nervous system. It is one of the most common neurological disorders around the world. There is still no complete cure for MS, and it remains entirely non-treatable disease with no effective treatment. Therefore, pharmaceutical companies and scientists are still searching for new drugs. In this context, bio-activity of olean-12-en-28-ol, 3β pentacosanoate (OPC) compound that we have isolated from Capparis ovata plant will be determined in vivo experimental allergic encephalomyelitis (EAE). EAE is the animal model of MS and is extensively used in the development of many drugs that are currently being used for the treatment of MS. Therefore, extensive and intensive studies will be carried out leading to the development of a novel therapeutic agent for MS.
First,
- chemical synthesis of OPC compounds will be carried to achieve the intended goals
- the purity and identity of the synthesized product will be confired
After , OPC will be applied to the EAE induced animals to determine its bioactivity along with Fingolimod (an oral drug currently used for MS) for comparative analysis. For this purpose,
- the expression levels of MS-associated genes
- isolation of cerebrospinal tissue infiltrating immune cells and their phenotypic analysis
- determination of autoimmune cytokines
- expression levels of MS-associated proteins
- inflammatory response-autoimmunity epigenetic analyzes
will be performed in those animals. Thus, the bio-efficiency potential of the OPC will be investigated extensively in a broad spectrum. In addition, potential target proteins of the OPC compound in the cells will be tried to describe. Therefore,
- OPC compound will be conjugated with biotin
- target proteins will be isolated using avidin-agarose affinity chromatography
- isolated proteins will be identified with nLC-MS/MS analysis.
For the first time, OPC compound was isolated from a natural resource and it’s in vitro efficacy for MS have been identified in our work previous studies (TUBITAK 112S187 project - unpublished data). Neither a study nor data was found with this compound in the literature. Preliminary research on the patent application for this compound has been completed, and the application has granted (Application No. 2015/10239). As a result, the project proposal is original and innovative.
Present project proposal covers both basic and analytical studies including determination of in vivo bio-efficiency of the OPC compound which is a highly probable new agent for the symptomatic treatment of MS. In this regard, our current proposal exhibits a solution oriented and innovative approaches to MS. The primary goal of this project proposal is to produce enough data for further pre-clinical and clinical studies to generate a national drug used in the treatment of MS by carrying out the essential and pioneering work for transition into clinical phase.
In addition, it is aimed at producing information for understanding the mechanism of the diseases by the methods to be used. Similarly, the data obtained from these studies will help to understand the disease by giving an opportunity for the identification novel molecular targets