DUAL FUNCTION PEPTIDE, DD-S052P, TREATMENT FOR MULTIDRUG RESISTANT BACTERIAL INFECTION: A PROMISING "FIRST-IN-CLASS" CANDIDATE DESIGNED TO COMBAT INFECTIOUS DISEASES

초록

Aim HLB Science has developed DD-S052P as a therapeutic candidate for the treatment of sepsis and multidrug-resistant bacterial infections. Background DD-S052P is a novel peptide antibiotic designed to maximize the interaction with lipopolysaccharide (LPS) and to resolve the global threat of antibiotic resistance. DD-S052P effectively binds to LPS and permeabilizes gram-negative bacterial membrane, resulting in strong antibacterial activities. It possesses potent therapeutic efficacy against gram-negative sepsis by LPS clearance and reduction of systemic infection-associated inflammation. Methods Sepsis rat models infected by extended spectrum betalactamase-producing E. coli and two types of carbapenem-resistant gram-negative bacteria were treated with varying doses of DDS052P via intravenous infusion. Direct bacterial counting in liver, lung and spleen was carried out. Serum LPS level and inflammatory cytokine levels in serum and organ were measured via limulus amebocyte lysate assay and enzyme-linked Immunosorbent assay, respectively. Non-clinical toxicology studies were designed as 2-week repeated dose toxicity studies and was used to establish the No Observed Adverse Effect Level (NOAEL). Results Results show that DD-S052P eliminated bacteria in organs and lowered LPS and inflammatory cytokine levels to those comparative to the non-infected control group. Based on these results, 50% Effective Dose (ED50) range of DD-S052P was estimated to be 0.25∼1.0 mg per kg per day. Essential non-clinical studies for 2-week repeated dose toxicity, genotoxicity and pharmacological safety have allowed NOAEL establishment without observation of toxic events and functional disturbances. Conclusions This study highlights the potential of DD-S052P as a promising safe peptide antibiotic for treating gram-negative sepsis.