Novel therapies for recessive dystrophic epidermolysis bullosa targeting at the COL7A1 promoter

• Project/Area Number: 25461681
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Dermatology
• Research Institution: Hokkaido University
• Principal Investigator: ARITA KEN 北海道大学, 医学(系)研究科(研究院), 客員研究員 (50374434)
• Co-Investigator(Kenkyū-buntansha): NOMURA Toshifumi 北海道大学, 北海道大学病院, 助教 (50399911) ; SHIMIZU Hiroshi 北海道大学, 医学(系)研究科(研究院), 教授 (00146672)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 表皮水疱症 / ７型コラーゲン

Outline of Final Research Achievements

No curative therapies for recessive dystrophic epidermolysis bullosa (RDEB) are currently available. In this study, we sought to develop novel therapies for this intractable disease targeting at the COL7A1 promoter. First, we constructed a vector containing the luc2P gene driven by the COL7A1 promoter and generated stable cell lines carrying the gene construct. Compound library screening using the stable cells identified a dozen of 'hits'. However, further screening showed that most of them are 'false-positive'. We are now testing these compounds using normal human epidermal keratinocytes to see if they up-regulate the COL7A1 promoter.

Research Products

• [Journal Article] Nodular morphoea: a first case associated with linear morphoea (2016)
  • Author(s): Nakazato S, Nomura T, Yamane N, Shinkuma S, Natsuga K, Fujita Y, Arita K, Shimizu H
  • Journal Title: Eur J Dermatol Volume: 26 Issue: 1 Pages: 95-96
  • DOI: 10.1684/ejd.2015.2656
  • Peer Reviewed
• [Journal Article] Genetic analysis of a novel splice-site mutation in TMC8 reveals the in-vivo importance of the TMC domain of TMC8. (2016)
  • Author(s): Miyauchi T, Nomura T, Suzuki S, Takeda M, Shinkuma S, Arita K, Fujita Y, Shimizu H.
  • Journal Title: British Journal of Dermatology Volume: in press Issue: 4 Pages: 803-806
  • DOI: 10.1111/bjd.14569
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Generalized acute subcutaneous edema as a rare cutaneous manifestation of severe dermatomyositis. (2015)
  • Author(s): Watanabe M, Natsuga K, Arita K, Abe R, Shimizu H.
  • Journal Title: Journal of European Academy of Dermatology and Venereology Volume: in press Issue: 11
  • DOI: 10.1111/jdv.13460
  • Peer Reviewed
• [Journal Article] Deep venous thrombosis in patients with Behcet's disease. (2015)
  • Author(s): Horie K, Izumi K, Nishie W, Nomura T, Nomura Y, Arita K, Shimizu H.
  • Journal Title: Journal of Dermatology Volume: 42 Issue: 1 Pages: 101-102
  • DOI: 10.1111/1346-8138.12741
  • Peer Reviewed / Open Access