| Project/Area Number |
16K19676
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Aichi Medical University |
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Principal Investigator |
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| Research Collaborator |
Kurahashi Hirokazu
Iwasa Masumi
Takahashi Eri
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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 |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | MCT8異常症 / reverse T3 / 早期診断 / 遺伝子治療 / Crispr/Cas9 / 甲状腺ホルモン / 輸送膜蛋白 / 先天性大脳白質形成不全症 / 精神運動発達遅滞 / MCT8 / Allan-Herndon-Dudley症候群 / AAV9 / LC-MS/MS |
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| Outline of Final Research Achievements |
MCT8 deficiency, one of the inherited thyroid disease, is developed due to loss of function of MCT8, which encode the membrane transporter of thyroid hormone. In this study, we investigated the early diagnosis of MCT8 deficiency and developed its neurological deficit model.
We confirmed that reverse T3 extracted from dried blood spot (DBS) at newborn age, could be measured by LC-MS/MS. Reverse T3 is one of the metabolite of thyroid hormone, which does not have thyroid hormone activity. We have collected 100 DBS from normal newborn and 5 DBS from the patients with MCT8 deficiency. We will measure the concentration of reverse T3 in these DBS and determine whether early diagnosis of MCT8 deficiency can be done using DBS at neonatal period. In addition, we obtained knockout mice produced by Crisper Cas9, which had the mution of insertion and/or deletion, resulting in frameshift. Now, we are investigating the phenotype of these mice.
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| Academic Significance and Societal Importance of the Research Achievements |
新生児濾紙血のreverse T3を測定することにより、MCT8異常症を症状が出現する前に診断できる可能性がある。現在は、MCT8異常症に対する根本的な治療法は存在しないが、将来的には遺伝子治療などで治療可能となる可能性があり、その際に早期診断法が存在すれば不可逆的な脳障害の発症を防ぐことができる。残念ながら、すでにMCT8異常症の症状が生じている確定診断例では、早期診断法が開発されても意義はほとんどない。
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