Chemical chaperone therapy for oculocutaneous albinism
| Project/Area Number |
16K10170
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Osaka City University |
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Principal Investigator |
Fukai Kazuyoshi 大阪市立大学, 大学院医学研究科, 登録医 (20244642)
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| 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)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| 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)
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| 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 |
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| 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.
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| 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。
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Report
(4 results)
Research Products
(20 results)
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[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.
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Journal Title
JAMA Dermatol.
Volume: 154
Issue: 7
Pages: 781-788
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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