2022 Fiscal Year Final Research Report
Establishment of novel fetal gene therapy for hypophosphatasia
| Project/Area Number |
19K18970
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 57020:Oral pathobiological science-related
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| Research Institution | Tokyo Dental College |
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Principal Investigator |
Takahashi Aki 東京歯科大学, 歯学部, 講師 (30778626)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | 低ホスファターゼ症 / 胎児治療 / 遺伝子治療 / アルカリホスファターゼ / 骨系統疾患 |
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| Outline of Final Research Achievements |
Under anesthesia,laparotomy was performed on maternal mice on days 15 to 18 of pregnancy,and AAV-eMCK-ALP prepared from the uterine membrane was intraperitoneally administered to fetuses for treatment. As a result,the treated HPP model mice developed normal weight gain,did not develop seizures,and the survival rate of treated mice was greatly improved compared to untreated HPP model mice.In addition,the increase in serum ALP activity and the improvement in malformation of the femur were confirmed.Furthermore,when the distribution of the AAV vector was confirmed,it was found to be highly expressed in the peritoneal membrane and muscle,but not so much in the liver.
When the maternal body was then observed,no particular abnormalities were confirmed,and pregnancy and childbirth were possible again after weaning offspring.
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| Free Research Field |
先天性の硬組織系統疾患の病態評価、治療実験
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| Academic Significance and Societal Importance of the Research Achievements |
従来のHPP治療法は開始時期が出生後であるため、胎生期に症状が進行し、死産となる
症例がある。安全な胎児遺伝子治療法の確立は、このような重症例の患者を治療することができ、臨床において非常に重要な意義をもつと考える。また、遺伝子診断技術の発展により、診断可能な遺伝病は増えている。しかし、治療法がないために人工妊娠中絶を選択する症例も多い。安全性が確認された胎児遺伝子治療法の確立は、HPPのみならず、他の重篤な遺伝病における治療の可能性が期待でき、臨床において大きな意義をもつ。さらに、胎児は血液脳関門や硬組織の形成が不十分であるため、治療酵素が行しやすい。そのため、投与量の減量が可能である。
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