Development of Fluorescent Probes for Highlighting Nerves During Image Guided Surgeries

开发图像引导手术期间突出神经的荧光探针

• 批准号: 10268248
• 负责人: Brett J. Berman
• 金额: $ 117.77万
• 依托单位: ALUME BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10268248
• 关键词: Amines; Amino Acids; Anatomy; Area; Binding; Biological Assay; California; Canis familiaris; Cephalic; Clinical; Clinical Trials; Color; Data; Development; Devices; Dissection; Distal; Dose; Drug Kinetics; Dyes; Ear; Erectile dysfunction; Evaluation; Excision; Eye; Facial nerve structure; Fluorescein; Fluorescence; Fluorescent Probes; Formulation; Future; Generations; Goals; Head and Neck Surgery; Human; Image; Image-Guided Surgery; Incidence; Incontinence; Infection; Injections; Injury; Intravenous; Investigational Drugs; Investigational New Drug Application; Label; Lead; Light; Lighting; Medical Imaging; Medical center; Methods; Microscope; Morbidity - disease rate; Motor; Mus; N-terminal; Nerve; Numbness; Operating Rooms; Operative Surgical Procedures; Outcome; Paralysed; Parathyroid gland; Patient-Focused Outcomes; Patients; Peptides; Pharmaceutical Preparations; Phase; Phase I/II Clinical Trial; Postoperative Period; Procedures; Prostate; Radical Prostatectomy; Rattus; Recurrent Laryngeal Nerve; Risk; Rodent; Safety; Salivary Gland Neoplasms; Sensory; Site; Small Business Innovation Research Grant; Spinal; Spine surgery; Sterility; Structure; Surgeon; Testing; Texture; Thyroid Gland; Tissues; Topical application; Toxic effect; Trauma; Tumor Cell Invasion; Universities; Urinary system; Urologic Surgical Procedures; Visual; Visualization; Water; afferent nerve; autonomic nerve; chronic pain; clinical candidate; clinical translation; cohort; design; imaging agent; imaging system; improved; in vivo; instrumentation; nerve injury; neurovascular; novel; phase 2 study; preservation; prevent; protein aminoacid sequence; reconstitution; research clinical testing; safety study; safety testing; success; tool

Abstract Fundamental goals of surgery are functional preservation and minimizing patient morbidity. Inadvertent nerve injury during surgery is a major cause of post-surgical patient morbidity due to the inability of surgeons to visualize nerves during surgery. Nerve injury during surgery can lead to chronic pain, numbness, permanent paralysis incontinence or erectile dysfunction. Current nerve identification during surgery utilizes non-quantifiable criteria such as anatomy, texture, color, and relationship to surrounding structures to distinguish nerves from non-nerve tissues. In instances of trauma, tumor invasion or infection, nerve identification using the above criteria can be especially challenging. Using white light reflectance, which is the standard mode of illumination in operating rooms, the visual difference between small nerves, such as distal branches of the facial nerve important during surgery for salivary gland neoplasms, or cavernosal nerves important during radical prostatectomy, and adjacent tissue can be imperceptible. There is an unmet need to improve the intraoperative visualization of nerves to preserve nerve function and minimize patient morbidity following surgery. There are currently no clinically approved agents to enhance nerve contrast during surgery. In this proposal, we aim to complete a Phase 1/2 clinical trial to test the safety and efficacy of a novel peptide dye conjugate (ALM-488) as an agent to aid visualization of nerves during surgery. ALM-488 is a peptide dye conjugate that has been shown to bind and highlight motor, sensory and autonomic nerves in-vivo. Alume anticipates that clinical translation of ALM-488 could be transformative for intraoperative visualization of nerves to prevent inadvertent injury during surgery thereby improving patient outcomes.

摘要 手术的基本目标是功能保留和最大限度地减少患者发病率。 手术过程中的无意神经损伤是术后患者发病的主要原因， 外科医生在手术中无法看到神经。手术中的神经损伤会导致 慢性疼痛、麻木、永久性瘫痪、失禁或勃起功能障碍。电流 手术期间的神经识别利用不可量化的标准，例如解剖结构，纹理， 颜色和与周围结构的关系，以区分神经和非神经组织。在 在创伤、肿瘤侵入或感染的情况下，使用上述标准的神经识别可以 特别具有挑战性。使用白色光反射，这是标准的照明模式 在手术室中，小神经之间的视觉差异，如远端分支的 唾液腺肿瘤手术中重要的面神经或海绵体神经 重要的是在根治性乳腺癌切除术，和邻近组织可以是察觉不到的。有一个 改善术中神经可视化以保护神经功能的需求未得到满足， 最大限度地减少术后患者发病率。目前没有临床批准的药物， 增强手术中的神经对比度。在这项提案中，我们的目标是完成1/2期临床试验， 测试新型肽染料缀合物（ALM-488）作为辅助剂的安全性和有效性的试验 在手术期间观察神经。ALM-488是一种肽染料缀合物， 以在体内结合和突出运动、感觉和自主神经。马林预计，临床 ALM-488的翻译对于神经的术中可视化可能是变革性的， 手术过程中的意外损伤，从而改善患者结局。