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Chemical chaperone therapy for oculocutaneous albinism

Research Project

Project/Area Number 16K10170
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionOsaka City University

Principal Investigator

Fukai Kazuyoshi  大阪市立大学, 大学院医学研究科, 登録医 (20244642)

Co-Investigator(Kenkyū-buntansha) 國本 浩之  大阪市立大学, 大学院医学研究科, 助教 (80372853)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords眼皮膚白皮症 / 遺伝性皮膚疾患 / ケミカルシャペロン / 色素異常症 / メラニン / 白皮症 / ライソゾーム病 / 小胞体 / チロシナーゼ / ミスセンス変異 / 常染色体劣性遺伝 / 視力障害
Outline of Final Research Achievements

Oculocutaneous albinism (OCA) is an autosomal recessive disease characterized by reduction or complete lack of melanin pigment in the skin, hair and eyes. In this study, we firstly investigated the intracellular localization of Japanese OCA1A missense mutants tyrosinase using immunohistochemical staining and western blotting. R77Q, R239W, D383N, P431L mutant tyrosinases retained within the ER, while H211Y mutant tyrosinases were partially transported to the Golgi apparataus. Secondly, we explored the possibility of chemical chaperone therapy for Japanese OCA1A missense mutants, and found that HeLa cells that express P431L tyrosinase mutant are able to retain the DOPA oxidase activity by the addition of a tyrosinase inhibitor in a dose-dependent manner. These results led to the conclusion that chemical chaperone therapy may be helpful for a fundamental treatment for OCA1 with P431L missense mutation.

Academic Significance and Societal Importance of the Research Achievements

今回の研究により、これまで治療方がなかった眼皮膚白皮症の治療法として、ケミカルシャペロン治療がすくなくともチロシナーゼ遺伝子の一部の変異による患者については有効であるということが理論的に証明された。今回の研究により、薬物の内服あるいは外用により、皮膚の色の回復、視力回復が期待できる可能性があることが示された。これは試験管内での成果であるので、動物実験で実際に有効であるのかどうか、検討していく必要がある。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (20 results)

All 2019 2018 2017 2016 Other

All Journal Article (10 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 10 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 3 results,  Invited: 1 results) Remarks (2 results)

  • [Journal Article] A case of anaphylaxis caused by black ginger in a dietary supplement2019

    • Author(s)
      Eriko Hayashi, Junko Sowa-Osako, Kazuyoshi Fukai, Aki Natsumi, Akiko Yagami, Nayu Sato, Naoshi Shimojo, Masashi Nakamura, Kayoko Matsunaga, Daisuke Tsuruta
    • Journal Title

      J Dermatol

      Volume: 46 Issue: 2

    • DOI

      10.1111/1346-8138.14592

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effectiveness of weekly paclitaxel for edema and pain in classic Kaposi sarcoma with widespread eruption in the lower legs2019

    • Author(s)
      Ohmura, Reina; Kamo, Riei; Fukai, Kazuyoshi; Ozawa, Toshiyuki; Awazawa, Ryoko; Ohsawa, Masahiko; Tsuruta, Daisuke; Kusutani, Nao
    • Journal Title

      J Dermatol

      Volume: 46 Issue: 5

    • DOI

      10.1111/1346-8138.14703

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The Molecular Basis of Chemical Chaperone Therapy for Oculocutaneous Albinism Type 1A2018

    • Author(s)
      Ayako Teramae, Yui Kobayashi, Hiroyuki Kunimoto, Koichi Nakajima, Tamio Suzuki, Daisuke Tsuruta and Kazuyoshi Fukai
    • Journal Title

      J Invest Dermatol

      Volume: 139 Issue: 5 Pages: 1143-1149

    • DOI

      10.1016/j.jid.2018.10.033

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Promising therapeutic option for cutaneous plasmacytosis: 308-nm excimer lamp.2018

    • Author(s)
      Omura R, Sowa-Osako J, Fukai K, Kusutani N, Takeoka Y, Koh H, Ohsawa M, Iwatsuki K, Tsuruta D, Hamada T.
    • Journal Title

      J Dermatol

      Volume: 45 Issue: 8

    • DOI

      10.1111/1346-8138.14262

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Presymptomatic genetic diagnosis of two siblings with hereditary angioedema,2018

    • Author(s)
      Kasami S, Sowa-Osako J, Fukai K, Tokimasa S, Kaga SI et al
    • Journal Title

      J Dermatol

      Volume: 45 Issue: 2

    • DOI

      10.1111/1346-8138.14103

    • Related Report
      2018 Annual Research Report 2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] A novel missense mutation of the STS gene in two siblings with X-linked ichthyosis, complicated by short stature, bone density reduction, epilepsy, and cryptorchidism2018

    • Author(s)
      A. Ohyama, H. Nakano, Y. Imanishi, T. Seto, D. Tsuruta, and K.Fukai
    • Journal Title

      Clin Exp Dermatol

      Volume: 44 Issue: 1 Pages: 78-79

    • DOI

      10.1111/ced.13741

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sirolimus Gel Treatment vs Placebo for Facial Angiofibromas in Patients With Tuberous Sclerosis Complex: A Randomized Clinical Trial.2018

    • Author(s)
      Wataya-Kaneda M,*, Ohno Y, Fujita Y, Yokozeki H, Niizeki H, Ogai M, Fukai K, Nagai H, Yoshida Y, Hamada I, Hio T, Shimizu K, Murota H.
    • Journal Title

      JAMA Dermatol.

      Volume: 154 Issue: 7 Pages: 781-788

    • DOI

      10.1001/jamadermatol.2018.1408

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Ultrastructural study of dyschromatosis symmetrica hereditaria with widespread2017

    • Author(s)
      Omura R, Fukai K, Sugawara K et al
    • Journal Title

      J Dermatol

      Volume: 44 Issue: 7

    • DOI

      10.1111/1346-8138.13849

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Case of chronic venous insufficiency-associated Kaposi's sarcoma in a Japanese2017

    • Author(s)
      Nishida M, Fukai K, Kamo R, Tsuruta D
    • Journal Title

      J Dermatol

      Volume: 44 Issue: 12

    • DOI

      10.1111/1346-8138.13989

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Probable allergic contact dermatitis from hydroquinone presenting as2017

    • Author(s)
      Yanagishita-Nakatsuji S, Fukai K, Ohyama A, Umekoji A, Sowa-Osako J, Tsuruta D
    • Journal Title

      J Dermatol

      Volume: 44 Issue: 12

    • DOI

      10.1111/1346-8138.14011

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] 眼皮膚白皮症におけるケミカルシャペロン療法の可能性について2018

    • Author(s)
      深井和吉、寺前彩子、鶴田大輔
    • Organizer
      日本皮膚科学会総会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] A basic in vitro study of novel therapy for oculocutaneous albinism type 12017

    • Author(s)
      Teramae A, Kobayashi Y, Fukai K, Kunimoto H, Nakajima K, Suzuki T, Tsuruta D
    • Organizer
      76th annual meeting of the Society of Investigative Dermatology
    • Place of Presentation
      Oregon Convention Center(アメリカ合衆国ポートランド)
    • Year and Date
      2017-04-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] A basic in vitro study of novel therapy for oculocutaneous albinism type 12017

    • Author(s)
      Fukai K, Teramae A, Kobayashi Y, Kunimoto H, Nakajima K, Suzuki T, Tsuruta D
    • Organizer
      分子皮膚科フォーラム
    • Place of Presentation
      ベルサール東京日本橋(東京都中央区)
    • Year and Date
      2017-04-14
    • Related Report
      2016 Research-status Report
  • [Presentation] A basic in vitro study of a novel therapy for oculocutaneous albinism type12017

    • Author(s)
      Fukai K, Teramae A, Kobayashi Y, et al
    • Organizer
      分子皮膚科フォーラム
    • Related Report
      2017 Research-status Report
  • [Presentation] A basic in-vitro study of novel therapy for oculocutaneous albinism type12017

    • Author(s)
      Teramae A, Kobayashi Y, Kunimoto H et al
    • Organizer
      Society for Investigative Dermatology 76th Annual Meeting.
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Molecular Basis Of Chemical Chaperone Therapy For2017

    • Author(s)
      Teramae A, Kobayashi Y, Kunimoto H et al
    • Organizer
      23rd International Pigment Cell Conference
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] Subcellular localization of tyrosinase of R77Q, H211Y, and P431L mutants in lentivirus transfected HeLa cell2016

    • Author(s)
      Teramae A, Kobayashi Y, Fukai K, Kunimoto H, Nakajima K, Suzuki T, Tsuruta D
    • Organizer
      第41回日本研究皮膚科学会
    • Place of Presentation
      仙台国際センター(宮城県仙台市)
    • Year and Date
      2016-12-09
    • Related Report
      2016 Research-status Report
  • [Presentation] Intracellular distribution of tyrosinase of R77Q, H211Y and P431L mutants2016

    • Author(s)
      Teramae A, Kobayashi Y, Fukai K, Kunimoto H, Nakajima K, Suzuki T, Tsuruta D
    • Organizer
      日本色素細胞学会
    • Place of Presentation
      岐阜大学サテライトキャンパス(岐阜県岐阜市)
    • Year and Date
      2016-11-12
    • Related Report
      2016 Research-status Report
  • [Remarks] 眼皮膚白皮症の病態解析と治療にむけた研究

    • URL

      http://www.med.osaka-cu.ac.jp/Derma/report/reports-03.shtml

    • Related Report
      2018 Annual Research Report 2016 Research-status Report
  • [Remarks] 白皮症・白斑の病態解明と治療法の開発

    • URL

      http://www.med.osaka-cu.ac.jp/Derma/report/reports-03.shtml

    • Related Report
      2017 Research-status Report

URL: 

Published: 2016-04-21   Modified: 2020-03-30  

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