Diabetes Mellitus (DM), a metabolic disorder characterized by defective insulin signaling and elevated bloodglucose, has become a public health epidemic with half of the US population diagnosed with either DM or pre-diabetes. One of the most common and devastating sequelae of uncontrolled DM is the development of chronicnon-healing wounds. An estimated 25% of diabetic patients develop chronic non-healing ulcers in their lifetimethat, given the poor vascularity and immunodeficiency associated with diabetes, are highly susceptible toinfection and frequently result in limb amputation. DM is currently the seventh leading cause of death in the U.S.Current management primarily focuses on controlling wound bioburden to promote wound healing, whichincludes pressure off-loading, antimicrobial medications and dressings, judicious wound care, and optimizationof lifestyle factors. However, complete wound closure is complicated by impairment of cellular migration andfunction in DM wounds. Therefore, there is a pressing need to develop novel therapeutic methods for diabeticwounds that directly restore the molecular and cellular processes required to promote proper cutaneous repair. Injuries in diabetic patients often persist and progress. Chronic DM causes significant alterations to severalphysiologic wound healing mechanisms that impair timely cell infiltration/migration, granulation tissue formation,and wound contraction. Based on more than 20 years of research on wound healing management, we havedeveloped a technologically innovative fibromodulin (FMOD)-based amino acid peptide sequence, SLI-F06, thatmarkedly stimulates fibroblast and endothelial cell migration and myofibroblast differentiation/contraction topromote timely wound closure. Previously, we demonstrated that SLI-F06 significantly promotes acute woundhealing without eliciting any adverse effects in preclinical animal studies at maximal feasible dosing as well asin ongoing Phase 1/2a clinical trial targeting acute wound healing. Excitingly, we have shown that repeated SLI-F06 administration significantly accelerates diabetic wound closure in a mouse model (NONcNZO10/LtJ) thatclosely simulates human type 2 DM. The goal of the current Fast-track SBIR application is to obtain the keypreclinical efficacy and mechanism of action data for SLI-F06 as a repeatedly administered, locallyapplied therapeutic for diabetic wounds for expanding the clinical indication of SLI-F06. Overall, thisproposal will accomplish key efficacy and mechanism of action (MOA) objectives to expedite commercializationof SLI-F06-based therapy for diabetic wounds. This product can significantly improve the quality of life of diabeticpatients suffering from chronic wounds that can lead to amputations and death.
Public Health Relevance Statement: PUBLIC HEALTH RELEVANCE
Up to 25% of diabetic patients develop chronic non-healing ulcers in their lifetime, which present significant
infection risks given the poor vascularity and immunodeficiency related to diabetes. More generally, chronic
non-healing wounds affect an estimated 6.5 Million Americans with annual cost of $50 billion dollars. This
project seeks to develop an effective, novel peptide-based treatment to promote wound healing and to improve
the quality of life for patients suffering from chronic wounds, especially in the diabetic populations.
Project Terms: Affect ; Amino Acids ; aminoacid ; Amputation ; Anatomy ; Anatomic ; Anatomic Sites ; Anatomic structures ; Anatomical Sciences ; Animals ; Blood Glucose ; Blood Sugar ; Blood Vessels ; vascular ; California ; Cause of Death ; cell motility ; Cell Locomotion ; Cell Migration ; Cell Movement ; Cellular Migration ; Cellular Motility ; Motility ; Cell physiology ; Cell Function ; Cell Process ; Cellular Function ; Cellular Physiology ; Cellular Process ; Subcellular Process ; Cells ; Cell Body ; Cicatrix ; Scars ; Clinical Research ; Clinical Study ; Clinical Trials ; Cessation of life ; Death ; Debridement ; Diabetes Mellitus ; diabetes ; Non-Insulin-Dependent Diabetes Mellitus ; Adult-Onset Diabetes Mellitus ; Ketosis-Resistant Diabetes Mellitus ; Maturity-Onset Diabetes Mellitus ; NIDDM ; Non-Insulin Dependent Diabetes ; Noninsulin Dependent Diabetes ; Noninsulin Dependent Diabetes Mellitus ; Slow-Onset Diabetes Mellitus ; Stable Diabetes Mellitus ; T2 DM ; T2D ; T2DM ; Type 2 Diabetes Mellitus ; Type 2 diabetes ; Type II Diabetes Mellitus ; Type II diabetes ; adult onset diabetes ; ketosis resistant diabetes ; maturity onset diabetes ; type 2 DM ; type II DM ; type two diabetes ; Diagnosis ; Sterile coverings ; Dressing ; Pharmaceutical Preparations ; Drugs ; Medication ; Pharmaceutic Preparations ; drug/agent ; Epidemic ; Extracellular Matrix ; Cell-Extracellular Matrix ; ECM ; Female ; Fibroblasts ; Goals ; Grant ; Granulation Tissue ; Human ; Modern Man ; Immunity ; Immunologic Deficiency Syndromes ; Immunodeficiency Disorder ; Immunodeficiency Syndrome ; Immunological Deficiency Syndromes ; hypoimmunity ; immune deficiency disorder ; immunodeficiency ; In Vitro ; Incidence ; Incubators ; Infection ; Institutes ; Lead ; Pb element ; heavy metal Pb ; heavy metal lead ; male ; Metabolic Diseases ; Metabolic Disorder ; Thesaurismosis ; metabolism disorder ; Methods ; Morbidity - disease rate ; Morbidity ; mortality ; Mus ; Mice ; Mice Mammals ; Murine ; United States National Institutes of Health ; NIH ; National Institutes of Health ; Patients ; Peptides ; Perfusion ; Peripheral Nervous System Diseases ; PNS Diseases ; Peripheral Nerve Diseases ; Peripheral Nervous System Disorders ; Peripheral Neuropathy ; pressure ; Privatization ; Production ; Public Health ; Quality of life ; QOL ; Recurrence ; Recurrent ; Research ; Resources ; Research Resources ; Safety ; Family suidae ; Pigs ; Suidae ; Swine ; porcine ; suid ; Testing ; Time ; Tissues ; Body Tissues ; United States Food and Drug Administration ; Food and Drug Administration ; USFDA ; Work ; wound healing ; Wound Repair ; wound resolution ; fibromodulin ; Outcome Measure ; Injury ; injuries ; base ; improved ; Area ; Chronic ; Clinical ; Phase ; Biological ; Histologic ; Histologically ; Physiological ; Physiologic ; Link ; Ensure ; Epithelial ; Endothelial Cells ; Myofibroblast ; diabetic ; Funding ; Therapeutic ; angiogenesis ; Infiltration ; scaffolding ; scaffold ; Prediabetes ; Prediabetic State ; pre-diabetes ; pre-diabetic ; prediabetic ; Prediabetes syndrome ; Recombinant Platelet Derived Growth Factor Beta Chain ; Regranex ; rhPDGF-BB ; Becaplermin ; Clinic ; Source ; fetal ; Allografting ; American ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; novel ; Diabetic wound ; diabetes ulcer ; diabetic skin wound ; diabetic ulcer ; Adverse effects ; peptide aminoacid sequence ; peptide sequence ; protein aminoacid sequence ; Skin ; Dose ; Defect ; Data ; Clinical Sciences ; lifestyle factors ; life-style factor ; Rodent Model ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Small Business Technology Transfer Research ; STTR ; Translational Research ; Translational Science ; translation research ; Molecular ; Development ; developmental ; pre-clinical ; preclinical ; cost ; insulin signaling ; nanosystems ; nano systems ; Outcome ; blood glucose regulation ; glucose control ; glucose homeostasis ; glucose regulation ; wound ; tissue wound ; wounding ; wounds ; Impaired wound healing ; Impaired tissue repair ; abnormal tissue repair ; delayed wound healing ; Population ; diabetic wound healing ; migration ; innovation ; innovate ; innovative ; Impairment ; antimicrobial ; anti-microbial ; novel therapeutics ; new drug treatments ; new drugs ; new therapeutics ; new therapy ; next generation therapeutics ; novel drug treatments ; novel drugs ; novel therapy ; mouse model ; murine model ; commercialization ; public health relevance ; primary outcome ; secondary outcome ; diabetic patient ; product development ; preclinical efficacy ; pre-clinical efficacy ; phase 2 study ; phase II study ; Regimen ; limb amputation ; amputated limb ; Microvascular Dysfunction ; microvascular complications ; microvascular disease ; small vessel disease ; chronic wound ; chronic skin wound ; Formulation ; Growth Factor ; Growth Agents ; Growth Substances ; Proteins Growth Factors ; mechanical properties ; wound closure ; non-healing wounds ; nonhealing wounds ; persistent wounds ; first-in-human ; first in man ; Infrastructure ; infection risk ; wound care ; wound assessment ; wound monitoring ; Phase I/II Clinical Trial ; Phase 1/2 Clinical Trial ; Skin repair ; cutaneous repair ; dermal repair ; chronic ulcer ; non-healing ulcer ; nonhealing ulcer ; acute wound ; epithelial wound ; porcine model ; pig model ; piglet model ; swine model ;
