Development of Human-Selective Nerve Illumination Peptide for Surgery

开发用于手术的人类选择性神经照明肽

• 批准号: 9788444
• 负责人: Quyen Nguyen
• 金额: $ 14.91万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-20 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9788444
• 关键词: Amino Acids; Anatomy; Animals; Binding; Clinical Trials; Clinical trial protocol document; Color; Development; Disease; Dissection; Distal; Dose; Dyes; Excision; Facial nerve structure; Fluorescein; Fluorescence; Fluorescent Dyes; Formulation; Generations; Glycoproteins; Goals; Human; Imagery; Infection; Injury; Investigational Drugs; Investigational New Drug Application; Label; Laboratories; Ligands; Light; Lighting; Link; Molecular; Molecular Target; Morbidity - disease rate; Motor; Nerve; Operating Rooms; Operative Surgical Procedures; Outcome; Parotid Neoplasms; Patient-Focused Outcomes; Patients; Peptides; Peripheral; Peripheral Nerves; Phage Display; Pharmacology; Pharmacology and Toxicology; Phase I Clinical Trials; Postoperative Period; Procedures; Publications; Radical Prostatectomy; Rodent; Salivary Gland Neoplasms; Singlet Oxygen; Specificity; Structure; Structure-Activity Relationship; Surgeon; Testing; Texture; Time; TimeLine; Tissues; Toxic effect; Toxicology; Trauma; Tumor Cell Invasion; United States Food and Drug Administration; Variant; Vertebral column; Visual; Work; afferent nerve; autonomic nerve; base; clinical development; clinical translation; cyanine dye 5; experience; human imaging; image guided; imaging agent; improved; neoplasm surgery; nerve injury; novel; off-label use; phase 1 testing; pre-clinical; preservation; prevent; protein aminoacid sequence; reconstruction; repaired; tool

Abstract A fundamental goal of surgery is function preservation and minimizing patient morbidity. Current nerve identification during surgery utilizes non-quantifiable criteria such as anatomy, texture, color, 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 may be challenging. Using white light reflectance, which is the standard mode of illumination in operating rooms, the visual difference between small nerves, such as cavernosal nerves important during radical prostatectomy or distal branches of the facial nerve important during surgery for salivary gland neoplasms, and adjacent tissue can be imperceptible. Our laboratory has extensive experience in developing molecularly targeted smart probes for surgical visualization of nerves. Recently, we have identified a novel peptide (HNP401) via phage display to have high level of human nerve binding. In this proposal, we aim to optimize HNP401 to enable its clinical translation for human surgery.

摘要 手术的一个基本目标是功能保护和最大限度地减少患者的发病率。 当前在手术期间的神经识别利用不可量化的标准，诸如解剖结构、纹理， 颜色，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，可以使用上述标准进行神经识别， 挑战性采用白色光反射，这是标准的照明模式， 房间，小神经之间的视觉差异，如海绵体神经重要期间 根治性切除术或在涎腺手术中重要的面神经远端分支 肿瘤和邻近组织可能是不可察觉的。我们的实验室拥有丰富的经验， 开发用于神经外科可视化的分子靶向智能探针。最近我们 通过噬菌体展示鉴定了具有高水平的人神经结合的新肽（HNP 401）。在 在这项提案中，我们的目标是优化HNP 401，使其能够用于人类手术的临床翻译。