A Novel Immunotoxin for Treatment and Cure of Strabismus

一种治疗和治愈斜视的新型免疫毒素

• 批准号: 6934390
• 负责人: LEO M CHALUPA
• 金额: $ 14万
• 依托单位: IMMUNOTOX, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6934390
• 关键词: Macaca; acetylcholine; anticholinergic agent; drug design /synthesis /production; drug screening /evaluation; eye coordination disorder; immunotoxicity; motor neurons; neurotoxins; nonhuman therapy evaluation; therapy design /development

The goal of this proposal is to develop a new treatment for strabismus, a visual disorder affecting 3-4% of the population, using a novel technology that we have recently formulated. This involves specific targeting and elimination of cholinergic motor neurons that innervate the extra-ocular muscles by injection of an antivesicular acetylcholine transporter-saporin (anti-VAChT-saporin). This approach offers some important advantages compared to corrective surgery (the most commonly employed procedure) as well as injections of botulinum toxin A (trade name Botox). Specific Aim 1 is to manufacture a new immunotoxin (termed IX-146) that will specifically target cholinergic neurons in the primate extraocular nuclei. In Specific Aim 2 we will assess the feasibility of using IX-146 for the treatment of strabismus. After injection of IX-146 into the lateral rectus muscle the resulting degree of strabismus will be measured using state of the art eye tracking methodologies. In Phase II of the project we will assess the efficacy of IX-146 treatment for strabismus. The use of IX-146 could be extended in the future to a wider variety of ophthalmologic, neurologic, and neuromuscular disorders, including blepharospasm as well as other types of dystonias.

该提案的目标是利用我们最近制定的新技术开发一种治疗斜视的新疗法，斜视是一种影响 3-4% 人口的视觉障碍。这涉及通过注射抗水泡乙酰胆碱转运蛋白皂草素（抗 VAChT-皂草素）来特异性靶向和消除支配眼外肌的胆碱能运动神经元。与矫正手术（最常用的手术）以及注射肉毒杆菌毒素 A（商品名 Botox）相比，这种方法具有一些重要的优势。具体目标 1 是制造一种新的免疫毒素（称为 IX-146），该毒素将专门针对灵长类动物眼外核中的胆碱能神经元。在具体目标 2 中，我们 将评估使用 IX-146 治疗斜视的可行性。将 IX-146 注射到外直肌后，将使用最先进的眼球追踪方法测量所产生的斜视程度。在该项目的第二阶段，我们将评估 IX-146 治疗斜视的疗效。 IX-146 的用途将来可以扩展到更广泛的眼科、神经系统和神经肌肉疾病，包括眼睑痉挛以及其他类型的肌张力障碍。