阿爾茨海默病治療藥物臨床試驗技術指導原則（試行）

為指導阿爾茨海默病藥物的科學研發和評價，提供可供參考的技術標準，藥審中心制定了《阿爾茨海默病藥物臨床試驗技術指導原則（試行）》（見附件）。

After more than ten years of exploration and research, we believe that the occurrence and development of Alzheimer’s disease (AD) is closely related to the decline of brain protein phosphatase (PP) function. The activity of PP decreases, the protein cannot be dephosphorylated and inactivated, the postsynaptic membrane continues to receive neurotransmitters released from the presynaptic membrane, and the signal channels cannot be closed in time, thus leading to the delay of nerve conduction and memory breakdown.

PP Agonist can improve the biological activity of PP and timely catalyze protein dephosphorylation to maintain normal neural activity. In addition, the increase of PP activity can also promote the dephosphorylation of Tau protein (P-tau), thereby avoiding the neurotoxicity and nerve cell death mediated by Tau hyperphosphorylation.

CRM-2102 is a PP2A agonist that has a strong excitatory effect on PP2A with impaired activity, and can significantly increase the biological activity of PP2A. Therefore, the development and research of PP2A agonist CRM-2102 may bring hope for the rehabilitation of AD.

Schematic diagram of pathological lesions in Alzheimer’s disease

根據美國藥品研究與制造商協會數據，1998-2017年有146個AD藥物以研究失敗告終，僅有四種藥品上市，臨床成功率僅2.7%。

2021年6月7日Aduhelm獲FDA批準上市后，因其臨床終點以Aβ代替， Aduhelm的上市之路飽受爭議，市場也表現慘淡。Aduhelm于2021年12月16日撤回了在歐盟的上市申請。

隨著GV-971國際三期臨床研究的提前中止，中國唯一的AD原研創藥物的出海之路也黯然退場。

雖然AD新藥相繼遇挫，但AD藥物市場是巨大的，這并不會影響人們對AD的有效治療藥物的持續探索。有理由相信人類終究會克服AD的！