[P3-109] Levels of SMN transcript and protein in fibroblasts derived from spinal muscular atrophy patients using thyrotropin releasing hormone
[Introduction] Most of spinal muscular atrophy (SMA) patients are caused by the loss of exon 7 in survival motor neuron (SMN) 1 gene, mapped to the telomeric site in chromosome 5q13 region. With increased copy number of SMN2 gene, which is almost identical to SMN1 gene and mapped to the centromere site in that region, increased SMN protein can ameliorate the phenotype in SMA patients. Some drugs including histone deacetylase inhibitors such as valproate, gene therapy and stem cell therapy are listed as SMA treatment strategy. [Methodology] Fibroblasts cell lines obtained from skin biopsy were established from 2 patients with SMA type 1 and 2 normal controls. We analyzed the levels of SMN transcript by quantitative RT-PCR and SMN protein by western blotting in the fibroblasts treated with a single dose of thyrotropin releasing hormone (TRH) ranging from 0.1 to 1.0 nM in 3 days and from 5 to 40 nM in 2 days. [Results] The levels of the SMN transcript and the SMN protein using TRH were increased by 1.2~1.9 folds in the lower concentration, and 1.0~2.0 folds in the lower one and 1.2~2.8 folds in the higher one compared to those without TRH, respectively. [Conclusions] The improvement of muscle weakness in the patients with SMA type 2,3 using TRH was found in some reports previously. The results of this study support the usefulness of TRH therapy in SMA patients.