Developing multi-specific aptamers for safe, potent, and long-lasting treatment of geographic atrophy

开发多特异性适体以安全、有效且持久地治疗地理萎缩

• 批准号: 10482569
• 负责人: Jinpeng Wang
• 金额: $ 24.76万
• 依托单位: APTITUDE MEDICAL SYSTEMS, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10482569
• 关键词: Acute; Adoption; Affect; Age related macular degeneration; American; Animal Model; Aptitude; Attention; Biological Assay; Blindness; COVID-19 pandemic; Cessation of life; Clinic; Clinical; Clinical Trials; Combined Modality Therapy; Complement; Complement Activation; Complement Membrane Attack Complex; Complement component C5; Development; Development Plans; Dose; Drug Kinetics; Eye; Funding; Genetic; Genetic study; Half-Life; Immune system; In Vitro; Incidence; Inferior; Inflammasome; Lasers; Lead; Legal; Letters; Maximum Tolerated Dose; Mediating; Methods; Modeling; Nucleic Acids; Oryctolagus cuniculus; Pathologic; Patients; Performance; Pharmaceutical Preparations; Phase; Process; Publishing; Reporting; Retina; Risk; Safety; Schedule; Signal Transduction; Small Business Innovation Research Grant; Structure; Study models; Testing; Therapeutic; Therapeutic Uses; Time; Tissues; Toxic effect; Vascular Endothelial Growth Factors; Vision; Work; age related; aptamer; arm; base; bevacizumab; complement pathway; compliance behavior; dosage; efficacy study; experience; geographic atrophy; improved; in vivo; innovation; interest; legally blind; meetings; neovascularization; novel; novel therapeutics; particle; phase I trial; phase III trial; pre-clinical research; preclinical development; preservation; prevent; programs; safety testing; standard care; systemic toxicity; therapeutic target

PROJECT ABSTRACT Geographic atrophy (GA) is a leading cause of blindness, affecting ~1.5 million Americans. There is currently no treatment for GA; in consequence, GA patients continually lose vision, and nearly half of them are legally blind. The complement pathway is part of the immune system and is activated by age-related pathologic changes in the eye. Extensive genetics studies, animal model studies, and clinical observations have established the complement pathway as the most promising therapeutic target for treating GA. Two late-stage anti-complement programs have both reported significant inhibition of GA progression, further substantiating the therapeutic potential of targeting complements. However, the current programs suffer from short duration and poor safety profile. Therefore, a safer and longer-lasting anti- complement program is clearly needed. The purpose of this SBIR project is to develop a multi-specific aptamer-based therapeutics that has the potential to overcome the limitation of existing anti-complement programs, and achieve safe, potent, and durable GA treatment for the first time. To that end, the Aptitude team has accumulated extensive experience in aptamer discovery. We have previously developed the Particle Display method that significantly improves the aptamer performance. We have also performed significant preliminary studies to prove the feasibility of constructing multi-specific aptamers. Our expertise in aptamer discovery is complemented by our collaborators’ expertise in GA preclinical research and clinical trials. If successful, this project has the potential of bringing a highly efficacious and long-acting treatment to GA patients.

项目摘要 地理萎缩 (GA) 是导致失明的主要原因，影响约 150 万美国人，目前尚无治疗方法。 对于 GA；因此，GA 患者视力不断丧失，其中近一半在法律上是失明的。 补体途径是免疫系统的一部分，由眼睛中与年龄相关的病理变化激活。 广泛的遗传学研究、动物模型研究和临床观察已经建立了补体途径： 两个晚期抗补体治疗方案均已报道。 显着抑制 GA 进展，进一步证实了靶向补体的治疗潜力。 目前的方案存在持续时间短、安全性差的问题，因此需要更安全、更持久的抗病毒方案。 显然需要补充计划。 该 SBIR 项目的目的是开发一种基于多特异性适配体的疗法，该疗法有可能克服 突破现有抗补体方案的局限性，首次实现安全、有效、持久的GA治疗。 为此，Aptitude团队在适配体发现方面积累了丰富的经验。 显着提高适配体性能的粒子显示方法我们也取得了显着的成果。 初步研究证明构建多特异性适体的可行性我们在适体发现方面的专业知识是。 如果成功，该项目将得到我们合作者在 GA 临床前研究和临床试验方面的专业知识的补充。 为 GA 患者带来高效、长效治疗的潜力。