Investigation the treatment efficiency of fingolimod derived novel ST-1505 compound in Multiple sclerosis

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Tezin Türü: Yüksek Lisans

Tezin Yürütüldüğü Kurum: Pamukkale Üniversitesi, Fen-Edebiyat Fakültesi, Biyoloji Bölümü, Türkiye

Tezin Onay Tarihi: 2019

Tezin Dili: Türkçe

Öğrenci: Fatma Sandal

Danışman: Alaattin Şen

Özet:

Multiple sclerosis (MS) is considered an autoimmune disease in the white matter of the brain, which is thought to induce an inflammatory cascade of T cells against myelin proteins and other unspecified antigens and is thought to be caused by demyelination and intense astrogliosis. Although the disease is still unknown, several environmental risk factors and genetic factors can be identified. An increased risk of developing MS is associated with environmental factors such as Epstein-Barr virus infection, smoking, high salt intake, vitamin D deficiency, and genetic factors, often associated with immune function.There is still no suitable treatment for MS today. Fingolimod is a structural analogue of natural sphingosis modulating the sphingosine 1-phosphate (S1P) receptor, the first oral drug approved by the FDA and approved by the disease. Fingolimod suppresses S1P receptors on lymphocytes, preventing the migration of lymphocytes from lymph nodes. Molecular gene expression variability analyzes were performed on SH-SY5Y and CCRF-CEM cells of Fingolimod (trade name Gilenya) derivative ST-1505.The administration of the ST-1505 compound at the dose of EC10 in the SH-SY5Y cell line resulted in 6.68; 1.66; 8.00; 6.75; 2.42; 5:54; 5:56; 1.85; 3:46; 7:11; 1.64 foldsuppression in the expression of the inflammatory cytokines CXCR3, TNF, CXCL9, HLA-DRB1, STAT3, C1S, CCL3, CD44, CSF1, IL10 and NFKB1, respectively.Similarly, the expression levels of IL-6, CXCR3, TNF, CXCL10, CXCL9, HLA-DRB1 and STAT3 genes at the same dose in the CCRF-CEM cell line were found to be 1.96; 6.68; 1.66; 2.15; 8.00; 6.75 and 2.42-fold suppressed. We are still working with CCRF- CEM cell linet o confirm the results. These results provided that the compound ST- 1505 had a good anti-inflammatory effect and was considered promising for the treatment of MS.