Antimicrobial peptide attacks acne

April 30, 2009

A new peptide has performed well in preclinical testing and could provide a potent antimicrobial punch against acne and, one day, methicillin-resistant Staphylococcus aureus, an expert says.

Hazleton, Pa. - A new peptide (Lipohexapeptide HB1345; Helix BioMedix) has shown potent anti-infective activity in animal and in vitro testing, according to several recent studies. Should it demonstrate similar clinical efficacy, it could provide a powerful treatment for acne and other skin conditions while avoiding antibiotic resistance, says an expert who reviewed five studies conducted by HB1345's patent holder.

"This new peptide shows very potent antibacterial activity against Propionibacterium acnes, with no evidence of resistance in preliminary studies. That's very exciting," says Stephen Schleicher, M.D., founder and medical director of DermDx Centers for Dermatology, Hazleton, Pa.

To evaluate HB1345's efficacy, Helix used a standard skin-abraded wound model in Spague-Dawley female rats. Researchers created one-inch square partial-thickness skin wounds on the back of each rat and contaminated each wound with approximately 2.5 x 10 5 colony-forming units (CFU) of S. aureus per wound.

At 30 minutes and at 12 hours post-infection, researchers applied 0.3 ml of a gel containing 1 percent HB1345. They continued this treatment for three days, then euthanized the rats and determined the number of remaining bacteria per gram of tissue. On day three, tissue from untreated control animals contained a mean of 7.89 (± 0.45) x 105 CFU, versus 2.53 (± 0.06) x 105 CFU for tissue from treated rats (P

"In a modified lipopolysaccharide binding assay, HB1345 quickly neutralized lipotechoic acid released by gram-positive bacteria, which can cause persistent, long-term inflammation," adds Dr. Schleicher. HB 1345 also showed 3.75 hours'’ post-application antibiotic effect against MRSA, and other testing showed that the peptide remains highly active in biophysical environments that mimic sebaceous gland secretions, which have proven hostile to other antimicrobial peptides such as LL-37.

Moreover, HB1345 showed potent antimicrobial activity with minimal inhibitory concentrations (MICs) of 0.5 to one mg/liter. And it works quickly - in one assay, it took 15 minutes to kill 99.9 percent of CFU in samples of lipids that mimic sebaceous gland secretions.

"Based on the data I reviewed," says Dr. Schleicher, "the efficacy is very strong. How this will pan out in practice will of course be determined by clinical trials. If the therapeutic result exceeds that of topical clindamycin, then this would be considered a valuable addition to current therapies." Initially, Helix will develop HB1345 for indications such as acne, rosacea and, through a novel barrier repair aspect, atopic dermatitis, according to a company press release. Dr. Schleicher postulates another role for the peptide, namely as a treatment for methicillin-resistant Staphylococcus aureus. "This is a very vexing problem, and newer treatment modalities are again most welcome," he says.

On August 6, Helix announced it had secured a U.S. patent for the family of hexapeptide antimicrobial agents including HB1345. The company is hoping HB1345 will perhaps be analogous to topical clindamycin. At press time, Helix was taking steps to move into clinical development in 2009.

Dr. Schleicher says he became interested in exploring therapeutic applications for peptides after testing an earlier Helix peptide, oligopeptide-10, which is now available in over-the-counter acne products including P.A.C. Perfect Acne Control System (Dermaventures LLC), which targets the Hispanic market. After seeing oligopeptide-10's efficacy against acne, he says, " encouraged Helix to keep working on other products that might demonstrate even greater efficacy," which he says HB1345 has done. DT


Disclosures:These studies were funded and performed by Helix BioMedix, Inc., which paid Dr. Schleicher to review its data. However, he possesses no financial interest in the company.


For more information:

www.aad.org

www.dermdx.com

www.helixbiomedix.com

www.dermaventures.com