SBIR-STTR Award

Fundamental goals of surgery are functional preservation and minimizing patient morbidity. 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. In this proposal, we aim to initiate commercialization of Human Nerve Targeting Peptide HNP-401-DC, a peptide dye conjugate identified to have high human nerve labeling in human tissue that highlights motor, sensory and autonomic nerve in animal models. HNP-401-DC should enable intraoperatively nerve highlighting in patients undergoing cancer resection or other surgeries thereby improving the surgeon’s ability to visualize nerves which will minimize inadvertent nerve injury.

Public Health Relevance Statement:
Narrative There is an unmet need to improve the intraoperative visualization of nerves to preserve nerve function and minimize patient morbidity following surgery. In this proposal, we aim to initiate commercialization of HNP-401- DC, a peptide dye conjugate that we identified to have high human nerve labeling and highlights motor, sensory and autonomic nerves. Guided surgery with a fluorescent dye conjugate of HNP-401-DC should enable intraoperatively nerve highlighting in patients undergoing cancer resection or other surgery thereby improving the surgeon’s ability to visualize nerves minimizing inadvertent nerve injury and patient morbidity.

NIH Spending Category:
Bioengineering; Biomedical Imaging; Biotechnology; Neurosciences

Project Terms:
Address; afferent nerve; Anatomy; Animal Model; Antibodies; autonomic nerve; Behavioral; Binding; Biodistribution; Biological Sciences; Blood; Body Weight decreased; C-terminal; cancer imaging; carboxyfluorescein; Chemistry; Clinical; Coagulation Process; Color; commercialization; Cysteine; Desire for food; Development; Distal; Drug Kinetics; Dyes; Epitopes; Excision; Excretory function; Facial nerve structure; FDA approved; Fluorescein; Fluorescence; Fluorescent Dyes; Fluorescent Probes; Formulation; Freeze Drying; Goals; Half-Life; Hematology; Hour; Human; human tissue; Image; Image-Guided Surgery; Imagery; imaging agent; improved; In Vitro; in vivo; Infection; Injury; innovation; innovative technologies; intravenous injection; Label; Legal patent; Light; Lighting; Liquid substance; Maleimides; Malignant Neoplasms; Measurement; Methods; Microscope; Morbidity - disease rate; Motor; Nerve; nerve injury; neurovascular; new technology; novel; off-patent; Operating Rooms; Operative Surgical Procedures; Outcome; Parathyroid gland; Pathology; Patient-Focused Outcomes; Patients; Peptides; Phage Display; Pharmacology; Phase; Postoperative Period; Preparation; preservation; prevent; Procedures; Production; Prostate; protein aminoacid sequence; Radical Prostatectomy; Recurrent Laryngeal Nerve; research clinical testing; Risk; Rodent; Salivary Gland Neoplasms; scale up; Sensory; Serum; Spine surgery; Structure; Surgeon; targeted agent; Technology; Testing; Texture; theranostics; Thyroid Gland; Tissues; tool; Toxic effect; Toxicology; Trauma; tumor; Tumor Cell Invasion; Urinary system; Validation; Vertebrates; Visual; Work

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.

Public Health Relevance Statement:
Narrative There is an unmet need to improve the intraoperative visualization of nerves to preserve nerve function and minimize patient morbidity following 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.

Project Terms:
afferent nerve; Amines; Amino Acids; Anatomy; Area; autonomic nerve; Binding; Biological Assay; California; Canis familiaris; Cephalic; chronic pain; Clinical; clinical candidate; clinical translation; Clinical Trials; cohort; Color; Data; design; 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; imaging agent; imaging system; improved; in vivo; Incidence; Incontinence; Infection; Injections; Injury; instrumentation; Intravenous; Investigational Drugs; Investigational New Drug Application; Label; Lead; Light; Lighting; Medical center; Medical Imaging; Methods; Microscope; Morbidity - disease rate; Motor; Mus; N-terminal; Nerve; nerve injury; neurovascular; novel; Numbness; Operating Rooms; Operative Surgical Procedures; Outcome; Paralysed; Parathyroid gland; Patient-Focused Outcomes; Patients; Peptides; Pharmaceutical Preparations; Phase; phase 2 study; Phase I/II Clinical Trial; Postoperative Period; preservation; prevent; Procedures; Prostate; protein aminoacid sequence; Radical Prostatectomy; Rattus; reconstitution; Recurrent Laryngeal Nerve; research clinical testing; Risk; Rodent; Safety; safety study; safety testing; Salivary Gland Neoplasms; Sensory; Site; Small Business Innovation Research Grant; Spinal; Spine surgery; Sterility; Structure; success; Surgeon; Testing; Texture; Thyroid Gland; Tissues; tool; Topical application; Toxic effect; Trauma; Tumor Cell Invasion; Universities; Urinary system; Urologic Surgical Procedures; Visual; Visualization; Water