漸凍人 (陽明大 鄭子豪) 瞄準Spt4 尋解藥! (amyotrophic lateral sclerosis and frontotemporal dementia)

漸凍人抑病基因找到了！ 最快2年有藥可用 健康醫療網 2016/09/18 (健康醫療網／記者郭庚儒報導) 漸凍人治療出現曙光！陽明大學研究發現，人體的「Spt4」蛋白質，能抑制漸凍人致病基因，成果登上國際頂尖期刊《科學》，目前已經投入新藥研發，最快2年內有新藥可用，可望延緩漸凍人病程。 全台約千名漸凍人 據統計，全台約有1000多名漸凍人，每年新增4、500人。陽明大學生化暨分子生物研究所所長鄭子豪指出，俗稱的漸凍人是一種神經退化性疾病的「肌萎縮性脊髓側索硬化症」（ALS）；一旦發病，就會逐漸失去運動的能力，最快2年內就會呼吸衰竭死亡。 找到抑病基因 鄭子豪所長表示，該研究團隊與美國史丹福大學、梅奧臨床醫院、麻省大學醫學院、賓州大學及科羅拉多大學波德分校合作，發現人體的「Spt4」蛋白質，能調控「C9ORF72」漸凍人致病基因，藉由抑制「Spt4」可減緩神經細胞的死亡。成果已發表在國際頂尖期刊《科學》。 2年有新藥可用 鄭子豪所長強調，研發證實，「Spt4」在核苷酸序列擴增造成的腦神經退化疾病，具有廣效性的運用。目前已投入藥物開發，最快2年內有新藥可用，可望延緩漸凍人的病程惡化程度。

Spt4 selectively regulates the expression of C9orf72 sense and antisense mutant transcripts Science  12 Aug 2016: An expanded hexanucleotide repeat in C9orf72 causes amyotrophic lateral sclerosis and frontotemporal dementia (c9FTD/ALS). Therapeutics are being developed to target RNAs containing the expanded repeat sequence (GGGGCC); however, this approach is complicated by the presence of antisense strand transcription of expanded GGCCCC repeats. We found that targeting the transcription elongation factor Spt4 selectively decreased production of both sense and antisense expanded transcripts, as well as their translated dipeptide repeat (DPR) products, and also mitigated degeneration in animal models. Knockdown of SUPT4H1, the human Spt4 ortholog, similarly decreased production of sense and antisense RNA foci, as well as DPR proteins, in patient cells. Therapeutic targeting of a single factor to eliminate c9FTD/ALS pathological features offers advantages over approaches that require targeting sense and antisense repeats separately.