一种用于图雷特综合征和其他运动障碍的新型PDE10A抑制剂
Randall D Marshall1, Frank S Menniti2,3, Mark A Tepper1
1EuMentis Therapeutics Inc., 275 Grove Street, 2-400, Newton, MA 02466, USA.
PDE10A抑制剂EM-221显示出对图雷特综合征治疗的前景. 临床前和人体研究表明其安全性,耐受性和向基底腺的能力,支持进一步的临床试验.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 运动障碍 运动障碍
背景情况:
- 图雷特综合征是一种神经发育障碍,与基底腺功能障碍有关.
- 固酶10A (PDE10A) 抑制剂正在为运动障碍治疗研究.
- 调节带状基底信号是关键的治疗策略.
研究的目的:
- 介绍PDE10A抑制剂EM-221的临床前和临床数据.
- 评估EM-221的安全性,耐受性和目标接触.
- 评估EM-221在治疗图雷特综合征和相关运动障碍方面的潜力.
主要方法:
- 在体外酶抑制试验测试以确定IC50和选择性.
- 动物研究 (老鼠) 评估行为影响和PDE10A抑制.
- 在老鼠和狗身上进行临床前毒理学研究.
- 人类安全性,耐受性和PET成像检测健康志愿者的条状酶占用率.
主要成果:
- EM-221证明了PDE10A的强大和选择性抑制 (IC50 = 9 pM).
- 在体内,EM-221在老鼠中显示出与PDE10A抑制相一致的效果.
- 在临床前毒理学和人类安全研究中,EM-221被耐受性良好.
- 在人体中,PET成像证实了显著的PDE10A条状酶占用率 (高达92.8%).
结论:
- EM-221具有良好的临床前和临床安全性和耐受性.
- 该药物有效地在人类大脑中激活其目标PDE10A.
- 这些发现支持EM-221进入图雷特综合征和其他运动障碍的第二阶段试验.
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