{"title":"Evaluation of Rosuvastatin Therapy on SIRT1 Gene Expression in Patients with Multiple Sclerosis: An Uncontrolled Clinical Trial","authors":"Shakiba Batoee Pharm.D , Maryam Etminaniesfahani Pham.D, Ph.D , Mehrdokht Mazdeh MD, Specialist in neurological diseases , Alireza Soltanian Ph.D , Fatemeh Nouri PharmD, PhD","doi":"10.1016/j.curtheres.2023.100718","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Multiple sclerosis (MS) is a chronic autoimmune disease. Current medications have some limitations such as low efficacy and high side effects. In recent years, statins have been raised as potential therapeutics for MS treatment with minimal complications. In addition, patient monitoring using suitable molecular markers is necessary for treatment response evaluation.</p></div><div><h3>Objective</h3><p>The aim of the present study was the evaluation of <em>SIRT1</em> gene expression changes following rosuvastatin therapy in patients with MS.</p></div><div><h3>Methods</h3><p>This before–after uncontrolled clinical trial study was performed on 25 patients with MS. Patients were treated with 20 mg rosuvastatin daily for 3 months. The Expanded Disability Status Scale (EDSS) was measured before and after statin therapy. Blood samples were taken from patients 2 times, before and after statin therapy, and centrifuged for white blood cell isolation. Total RNA was extracted using RNX-plus reagent, and complementary DNA was synthesized using Pars Tous cDNA Synthesis Kit. Real-time polymerase chain reaction was done using SYBR blue master mix and gene-specific primers in Roche light cycler. Patients’ information was recorded using a checklist. Data analysis was performed using SPSS version 23 and Graph Pad version 9 software and <em>P</em> < 0.05 was considered a significant level.</p></div><div><h3>Results</h3><p><em>SIRT1</em> was significantly upregulated in MS patients after statin therapy. Subsequently, EDSS of patients was decreased along with the increase in <em>SIRT1</em> gene expression, although EDSS changes were not significant (<em>P</em> > 0.05). Pearson correlation test showed no significant relationship between EDSS and <em>SIRT1</em> gene expression (<em>P</em> > 0.05). No significant relationship was observed between <em>SIRT1</em> expression or EDSS levels with patients’ age, sex, weight, height, and body mass index and administrated drugs (<em>P</em> > 0.05).</p></div><div><h3>Conclusions</h3><p><em>SIRT1</em> potentially is a sensitive and reliable biomarker for patients with MS monitoring during statin therapy.</p></div>","PeriodicalId":10920,"journal":{"name":"Current Therapeutic Research-clinical and Experimental","volume":"99 ","pages":"Article 100718"},"PeriodicalIF":1.6000,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0011393X23000279/pdfft?md5=71c227af18d89c05bd8f555795416d6f&pid=1-s2.0-S0011393X23000279-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Therapeutic Research-clinical and Experimental","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0011393X23000279","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Background
Multiple sclerosis (MS) is a chronic autoimmune disease. Current medications have some limitations such as low efficacy and high side effects. In recent years, statins have been raised as potential therapeutics for MS treatment with minimal complications. In addition, patient monitoring using suitable molecular markers is necessary for treatment response evaluation.
Objective
The aim of the present study was the evaluation of SIRT1 gene expression changes following rosuvastatin therapy in patients with MS.
Methods
This before–after uncontrolled clinical trial study was performed on 25 patients with MS. Patients were treated with 20 mg rosuvastatin daily for 3 months. The Expanded Disability Status Scale (EDSS) was measured before and after statin therapy. Blood samples were taken from patients 2 times, before and after statin therapy, and centrifuged for white blood cell isolation. Total RNA was extracted using RNX-plus reagent, and complementary DNA was synthesized using Pars Tous cDNA Synthesis Kit. Real-time polymerase chain reaction was done using SYBR blue master mix and gene-specific primers in Roche light cycler. Patients’ information was recorded using a checklist. Data analysis was performed using SPSS version 23 and Graph Pad version 9 software and P < 0.05 was considered a significant level.
Results
SIRT1 was significantly upregulated in MS patients after statin therapy. Subsequently, EDSS of patients was decreased along with the increase in SIRT1 gene expression, although EDSS changes were not significant (P > 0.05). Pearson correlation test showed no significant relationship between EDSS and SIRT1 gene expression (P > 0.05). No significant relationship was observed between SIRT1 expression or EDSS levels with patients’ age, sex, weight, height, and body mass index and administrated drugs (P > 0.05).
Conclusions
SIRT1 potentially is a sensitive and reliable biomarker for patients with MS monitoring during statin therapy.
背景:多发性硬化症(MS)是一种慢性自身免疫性疾病。目前的药物存在疗效低、副作用大等局限性。近年来,他汀类药物被认为是治疗多发性硬化症的潜在药物,其并发症很少。此外,患者监测使用合适的分子标记是必要的治疗反应评估。目的探讨瑞舒伐他汀治疗多发性硬化症后SIRT1基因表达的变化。方法25例ms患者接受瑞舒伐他汀治疗3个月,每日20 mg。在他汀类药物治疗前后测量扩展残疾状态量表(EDSS)。患者在他汀类药物治疗前后各取2次血样,离心分离白细胞。用RNX-plus试剂提取总RNA,用Pars Tous cDNA Synthesis Kit合成互补DNA。采用SYBR蓝色基质和基因特异性引物在罗氏光循环器上进行实时聚合酶链反应。使用检查表记录患者信息。数据分析采用SPSS version 23、Graph Pad version 9软件和P <0.05为显著水平。结果sirt1在MS患者接受他汀类药物治疗后显著上调。随后,患者的EDSS随着SIRT1基因表达的增加而降低,但EDSS变化不显著(P >0.05)。Pearson相关检验显示,EDSS与SIRT1基因表达无显著相关性(P >0.05)。SIRT1表达或EDSS水平与患者的年龄、性别、体重、身高、体重指数和给药之间无显著关系(P >0.05)。结论sirrt1可能是一种敏感可靠的生物标志物,可用于他汀类药物治疗期间MS患者的监测。
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