Development of early diagnosis of MCT8 deficiency and the efficacy of gene therapy using animal model of neurological defect

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K19676
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Aichi Medical University
• Principal Investigator: Hideyuki Iwayama Iwayama 愛知医科大学, 医学部, 講師 (00757726)
• Research Collaborator: Kurahashi Hirokazu ; Iwasa Masumi ; Takahashi Eri
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: MCT8異常症 / reverse T3 / 早期診断 / 遺伝子治療 / Crispr/Cas9

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.

Free Research Field

小児内分泌

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。