A Novel Class of Topical Pleitropic Anti-Acne Therapeutics

Information

  • Research Project
  • 7999672
  • ApplicationId
    7999672
  • Core Project Number
    R43AR060102
  • Full Project Number
    1R43AR060102-01
  • Serial Number
    60102
  • FOA Number
    PA-09-080
  • Sub Project Id
  • Project Start Date
    9/1/2010 - 14 years ago
  • Project End Date
    8/31/2011 - 13 years ago
  • Program Officer Name
    CIBOTTI, RICARDO
  • Budget Start Date
    9/1/2010 - 14 years ago
  • Budget End Date
    8/31/2011 - 13 years ago
  • Fiscal Year
    2010
  • Support Year
    1
  • Suffix
  • Award Notice Date
    8/27/2010 - 14 years ago
Organizations

A Novel Class of Topical Pleitropic Anti-Acne Therapeutics

DESCRIPTION (provided by applicant): Acne is a multifactorial disease affecting ~50 million people in the US. Three main factors contribute to the pathogenesis of acne;1) P. acnes growth 2) P. acnes-induced inflammation and 3) overproduction of sebum, all targets for therapeutic intervention. Treatments, such as antibiotics and benzylperoxide (BPO) are directed at the bacterium P. acnes and retinoids target sebum control. Several antimicrobial and retinoids also possess anti-inflammatory activity. However, to date a treatment directed at all three components of acne has not been identified. Signum's isoprenylcysteine (IPC) analogs represent a novel class of topical therapeutics that potentially targets all three contributors of acne pathology. Our preliminary results demonstrate IPC analogs inhibit P. acnes growth. In addition, when topically applied, using an in vivo irritant-dermatitis inflammatory model, our results demonstrate IPC analogs have strong anti-inflammatory activity inhibiting neutrophil infiltration, edema and erythema of the skin. Preliminary results support a mechanism involving the reduction in keratinocyte inflammatory mediator production. We have extended these observations to in vitro and in vivo P. acnes-induced inflammation models, demonstrating IPC inhibition of several pro-inflammatory cytokines. Lastly, IPC analogs have also been shown to modulate GPCR signaling, suggesting a potential role in regulating sebum control through inhibition of the GPCR melanocortin 5 receptor (MC5R) (critical for sebaceous gland lipogenesis). Based on our previous work, we hypothesize by screening our library of IPC compounds we will be able to identify IPC chemotypes with plieotropic effects to be developed as a novel therapeutic for acne. Structure-activity relationship of these results will lead to proof of principle by identifying, designing and testing candidate compound(s) having the highest combined potency towards each pathological factor, which will be subsequently developed in a Phase II application. PUBLIC HEALTH RELEVANCE: Acne is the most common disorder of the human skin and affects up to 80% of individuals in their lives. Three main factors contributing to the pathogenesis of acne are 1) P. acnes growth 2) P. acnes-induced inflammation and 3) overproduction of sebum all of which are potential targets for therapeutic intervention. To date a treatment directed at all three components of acne has not been identified. Successful development of this novel class of topical therapeutics will be the first that potentially target all three contributors of acne pathology.

IC Name
NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES
  • Activity
    R43
  • Administering IC
    AR
  • Application Type
    1
  • Direct Cost Amount
  • Indirect Cost Amount
  • Total Cost
    327178
  • Sub Project Total Cost
  • ARRA Funded
    False
  • CFDA Code
    846
  • Ed Inst. Type
  • Funding ICs
    NIAMS:327178\
  • Funding Mechanism
    SBIR-STTR
  • Study Section
    ZRG1
  • Study Section Name
    Special Emphasis Panel
  • Organization Name
    SIGNUM BIOSCIENCES
  • Organization Department
  • Organization DUNS
    144196354
  • Organization City
    MONMOUTH JUNCTION
  • Organization State
    NJ
  • Organization Country
    UNITED STATES
  • Organization Zip Code
    088521921
  • Organization District
    UNITED STATES