İnvestigation of MİR-155-5P, MİR-222-5P AND MİR-378B potential biomarkers in the follow-up pediatric spinal muscular atrophy (SMA) pati̇ents receiving nusi̇nersen treatment

Aim: In this thesis, the first target was to identify miRNAs expressed in muscle and capable of targeting SMN2-exon 7 by in silico analysis. Next, it is aimed to obtain an information/indicator of Nusinersen performance by investigating the profiles of miRNAs that we spend in the Cerebrospinal Fluid (CSF) of SMA patients before and after Nusinersen capacity. Method: As a result of in silico analysis, three miRNAs (miR-155-5p, miR-222-5p, and miR-378b) were identified, both expressed in muscle and highly correlated with SMN2-exon7. 20 pediatric patients diagnosed with SMA were included in the study and before and after each Nusinersen administration, the expression of expressions with RT-PCR was analyzed by isolation of the miRNAs determined in 48 5ml CSF sample taken from the patients. Significance analysis of the difference in miRNA expression between before and after each Nusinersen administration was performed and correlated with patients' clinical parameters and HFMSE scores, which provide information about the treatment response of SMA patients in particular. In addition, the effect of Nusinersen on miRNA profile changes according to SMA types was evaluated. Results: HFMSE score was found to increase with Nusinersen treatment according to the first situation. When the expression level of miR-222-5p was examined, there was an increase between CSF1 and CSF2 measurements close to significance (p = 0.068). At the expression level of miR-378b, there was a difference close to significance between CSF1 and CSF3 measurements (p = 0.068). HFMSE scores and miR-222-5p and miR-378b expressions were compared, but no correlation was found. However, when we look at the first and final status comparisons, it was found that both HFMSE and miR-222-5p and miR-378b increased over time (according to the first situation). With the change of HFMSE, there was a negative statistical correlation between miR-222-5p and miR-378b Conclusion: These non-coding RNA miRNAs, together with Nusinersen, are promising as potential biomarkers for better disease prevention, progression and capabilities of therapeutic response. Our study will be an idea of the studies to be carried out in SMA patients receiving Nusinersen treatment of MIRNAs, to better understand, progress and monitor the therapeutic response of the disease.