D. EF-005對抗阿茲海默症

阿茲海默症iPS 幹細胞篩選出治療之新穎小分子藥物 

Small molecule (EF-005) against Alzheimer’s disease discovery by using disease iPS cell 

“Small molecular(EF-005) γ-secretase inhibitor”
近期即將申請美國 FDA與台灣TFDA “ IND”
尋求合作開發伙伴包含藥廠及創投

      阿茲海默症是一種腦神經元的退化性疾病,臨床上的主要表現是短期記憶及語言缺失伴隨憂鬱與躁鬱情緒;程度嚴重時會遺忘基本生活與行動能力,終至死亡。 小分子藥物-謬思 (EF-005);經動物正子掃描後治療後3xTg小鼠及阿茲海默症iPS細胞發現可有效減少引發阿茲海默症的可能成因;包含類澱粉蛋白堆積以及濤蛋白的分布及磷酸化異常。另外在帶有阿茲海默症基因的模式3xTg小鼠實驗得到證實可明顯改進記憶,機miR-29b-能夠負向調節PSEN2(g-secretase subunit)表達,已申請全球專利,目前本產品已完成原料藥GMP生產、製劑生產與檢驗分析、GLP毒理試驗、安全性藥理試驗、PK、PD試驗等項目,近期即將申請美國 FDA與台灣TFDA進行試驗性新藥登記。我們將尋求合作開發伙伴包含藥廠及創投

      Alzheimer’s disease (AD) is a degenerative disease of brain neurons, with its main clinical manifestations as short-term memory and language loss accompanied by depression; when serious, the basic life and mobility will be forgotten, resulting in eventual death. The small molecular EF005 developed by the Tzu Chi Medical Foundation and National Chung Hsing University has been found to be effective in reducing the possible causes of Alzheimer’s disease; it includes amyloid accumulation and distribution and phosphorylation abnormalities by animal PET in 3xTg transgenic mice and iPS cells derived from AD patient. In addition, it also demonstrates significant improvement on the memory in 3xTg transgenic mice. The molecular targeting is PSEN2 gene mediated by miR-29b-3p(g-secretase subunit). The global patent has been applied. At present, EF005 has been performed a GMP grade production accompanied by finished GLP toxicology, safety pharmacology, pharmacokinetics and pharmacodynamics study. Registration of the new experimental drug for the US FDA and Taiwan TFDA will be applied for. We will seek for collaboration in venture capital or in an international pharmaceutical company. 

EF-005能夠有效降低類澱粉蛋白

細胞加入EF-005藥物後,神經細胞(綠色)周圍可以發現 類澱粉蛋白沉積情形有明顯差異(紅色)

EF-005能夠有效降低濤蛋白(Tau)異位的現象

加入EF-005藥物後Tau蛋白異位的數量差異(紅色箭頭) 

偵測阿茲海默症動物模式的腦部之類澱粉蛋白沉積情形可見EF-005藥物的明顯效用 

      使用類澱粉蛋白酶追蹤試劑(18F-Florbetaben;FBB)透過正子電腦斷層掃描(Positron emission tomography;PET/CT)檢測帶阿茲海默症基因的動物模式-3xTg mice,顏色越偏橘紅色代表類澱粉蛋白堆積越多。 

行為檢測顯示EF-005藥物能夠有效幫助記憶 

      動物實驗以會產生阿茲海默症之基因轉殖鼠-3xTg mice進行行為檢測。經過五天記憶訓練後,未給予藥物治療的小鼠一定時間內無法找到紫色圓圈所標示的平台。有給予藥物的小鼠能夠在一定時間內找到的休息平台(紅色標示為小鼠停留終點)。