Development of an ophthalmic diagnostic probe for neurodegenerativedisorders

开发神经退行性疾病眼科诊断探针

• 批准号: 9357487
• 负责人: Stella Sarraf
• 金额: $ 21.12万
• 依托单位: AMYDIS DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-30 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9357487
• 关键词: Alzheimer' s Disease; Amyloid; Amyloid deposition; Amyloidosis; Animals; Binding; Brain; Cadaver; Clinic; Clinical; Computer software; Dementia; Deposition; Development; Diagnosis; Diagnostic; Diagnostic Imaging; Diagnostic Procedure; Diagnostic tests; Disease; Disease Progression; Dose; Early Diagnosis; Evaluation; Eye; Eye diseases; Family; Fluorescent Probes; Formulation; Human; Image; Image Analysis; Imagery; Impaired cognition; Individual; Intravenous; Kilogram; Label; Methods; Modeling; Monitor; Morphology; Mus; Neuraxis; Neurobehavioral Manifestations; Neurodegenerative Disorders; Neurons; Optical Methods; Oryctolagus cuniculus; Pathogenesis; Pathology; Patients; Pharmacologic Substance; Phase; Prions; Process; Property; Reporting; Research; Retina; Retinal; Senile Plaques; Signal Transduction; Small Business Innovation Research Grant; Sodium Chloride; Solid; Staining method; Stains; Symptoms; Technology; Testing; Tissues; Topical application; Toxicology; Translating; Translations; age related; amyloid imaging; animal imaging; base; biophysical properties; clinical application; clinical development; crystallinity; density; design; disease diagnosis; drug candidate; effective therapy; experimental study; fluorescence imaging; human tissue; in vivo; mouse model; novel; physical property; protein aggregate; research clinical testing; small molecule; tool; tool development

Project Summary Deposition of amyloid plaques in the brain represents a universal feature Alzheimer’s disease pathology and precedes clinical symptoms by several years. Currently, diagnosis of amyloid-associated dementias in individuals showing symptoms of cognitive decline is extremely difficult, requiring multiple modes of testing over months to years. Early, pre-symptomatic diagnosis is even more challenging, if not impossible, with currently available technology. A non-invasive method for diagnosing Alzheimer’s disease is greatly needed. We will further evaluate the use of AMDX-201, a novel fluorescent probe that can label amyloids in tissue, as a diagnostic for Alzheimer’s disease. AMDX-201 has been shown to fluorescently label AD-related deposits in vivo. Importantly, this probe has also been shown to effectively image amyloid deposits in the retina of AD- mice following both topical and intravenous dosing. The properties of AMDX-201 are ideal for its development as a topical diagnostic probe for AD. The studies outlined in this proposal advance AMDX-201 to the Pre-IND stage. The synthesis of AMDX-201 will be optimized through dedicated process development activities. A formulation effective for topical administration in humans will be developed along with in vivo evaluation of diagnostic efficacy in two species of animals. Further, the retinal images obtained throughout formulation development will be utilized to develop a method to quantify the number, size and intensity of amyloid deposits. Together, the aims of this proposal will result in an optimized diagnostic product capable of imaging AD in the retina. The diagnostic product will be advanced to the point of being ready for IND-enabling Toxicology studies.

项目概要 大脑中淀粉样斑块的沉积代表了阿尔茨海默氏病病理学的普遍特征， 目前，淀粉样蛋白相关痴呆的诊断要早于临床症状数年。 表现出认知能力下降症状的个体是极其困难的，需要多种模式的测试 就目前而言，早期症状前诊断即使不是不可能，也更具挑战性。 非常需要一种诊断阿尔茨海默病的非侵入性方法。 我们将进一步评估AMDX-201的使用，这是一种可以标记组织中淀粉样蛋白的新型荧光探针， AMDX-201 已被证明可以荧光标记 AD 相关沉积物，用于诊断阿尔茨海默病。 重要的是，该探针还被证明可以有效地对 AD-视网膜中的淀粉样沉积物进行成像。 AMDX-201 的特性非常适合其开发。 作为 AD 的局部诊断探针，该提案中概述的研究将 AMDX-201 推进至 Pre-IND 阶段。 AMDX-201 的合成将通过专门的工艺开发活动进行优化。 将开发人类局部给药的制剂有效性以及体内评价 此外，在整个配制过程中获得的视网膜图像的诊断效果。 该开发将用于开发一种量化淀粉样蛋白沉积物的数量、大小和强度的方法。 总之，该提案的目标将是产生一种能够在 AD 中进行成像的优化诊断产品。 该诊断产品将进入准备进行 IND 毒理学研究的阶段。