UCLA researchers in the Departments of Dentistry and Plastic Surgery have developed a novel suppressor of Npas2 for the regeneration of connective tissues.
BACKGROUND:
Open wounds of the skin and oral cavity are subject to infection and scarring if not properly closed. Patients may experience a variety of social consequences due to unclosed wounds of the face and head, which are among the most common regions for injury or disease. Specifically, periodontitis in the oral cavity causes an open space between gingiva and the tooth surface that requires closure. Almost half of the adult dentate population presents with periodontitis, and periodontitis is also the most common clinical disease in dogs. Therefore, there is a large unmet veterinary and human patient need for wound healing of periodontitis. Current approaches for facial and oral wound healing are sutures or adhesives. However, these techniques have been practiced for decades with minimal innovation and improvement. Recent findings have demonstrated a connection between circadian rhythm and capacity for tissue regeneration. Identification of circadian clock genes directly involved tissue regeneration represent novel therapeutic targets for wound healing.
INNOVATION:
A novel suppressor of Npas2 was discovered for accelerated dermal wound healing and periodontal connective tissue regeneration. Npas2 is a circadian clock gene, that UCLA researchers have identified to regulate skin wound healing. A therapeutic suppressor of Npas2 has demonstrated regeneration of tissue and alveolar bone in mice, for the treatment of periodontal disease. This Npas2 suppressor has been repurposed for connective tissue regeneration as it is already FDA approved for the treatment of mild to moderate hypertension. Alternative approaches for wound healing, including sutures and adhesives, may require more recovery time and have greater potential for scarring compared to treatment with this compound. This innovative Npas2 suppressor will satisfy a large unmet need for periodontal disease therapeutics in both human and veterinary patients.
POTENTIAL APPLICATIONS:
• Dermal wound regeneration following trauma or chronic inflammation
• Connective tissue regeneration including alveolar bone
ADVANTAGES:
• Therapeutic suppression of Npas2 leads to enhanced wound healing and periodontal tissue regeneration
• Compound for Npas2 suppression is already FDA approved for the treatment of mild to moderate hypertension
• Compound demonstrates accelerated wound healing compared with other applications
• Less invasive treatment for wound closure/healing compared to traditional sutures and adhesives
DEVELOPMENT-TO-DATE:
This compound has been shown to regenerate periodontal connective tissue and alveolar bone in mouse models of periodontitis, through effective suppression of Npas2. Further, the compound accelerated dermal wound healing in mouse dorsal skin.
RELATED PAPERS
Subbiah N, Campagna J, Spilman P, Alam MP, Sharma S, Hokugo A, Nishimura I, John V. Deformable Nanovesicles Synthesized through an Adaptable Microfluidic Platform for Enhanced Localized Transdermal Drug Delivery. J Drug Deliv. 2017;2017:4759839. doi: 10.1155/2017/4759839. PubMed PMID: 28480080; PMCID: PMC5396447.
Sasaki H, Hokugo A, Wang L, Morinaga K, Ngo JT, Okawa H, Nishimura I. Neuronal PAS Domain 2 (Npas2)-Deficient Fibroblasts Accelerate Skin Wound Healing and Dermal Collagen Reconstruction. Anat Rec (Hoboken). 2019. doi: 10.1002/ar.24109. PubMed PMID: 30851151.