Is Parkinson's disease lysosomal disease? A large-scale clinical and genetic approach
| Project/Area Number |
19K17047
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 52020:Neurology-related
|
|---|
| Research Institution | Juntendo University |
|---|
Principal Investigator |
Ogaki Kotaro 順天堂大学, 医学部, 非常勤講師 (20459035)
|
|---|
| Project Period (FY) |
2019-04-01 – 2023-03-31
|
| Project Status |
Completed (Fiscal Year 2022)
|
| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2020: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
|
|---|
| Keywords | パーキンソン病 / 遺伝子 / リソソーム病 / 神経科学 / 次世代シーケンサー / 脳神経内科 / 神経内科 |
|---|
| Outline of Research at the Start |
パーキンソン病(PD)の病態解明を目的とした原因遺伝子の同定は当該研究領域に飛躍的な進歩をもたらしたが、遺伝子スクリーニングでは陽性率は高々25％内外で未だ変異が決定されていない症例が殆どである。近年リソソーム病(Lysosomal storage disorders: LSD)の1つであるゴーシェ病を引き起こすGBA遺伝子がPDの最も重要なリスク感受性遺伝子の１つとして報告され、GBAの病態に沿ったプレシジョンメディスンの開発に繋がっている。申請者は家族性PDの大規模サンプルにて54のLSD原因遺伝子を網羅的に解析し、更なる新規PD関連遺伝子を単離し、PD病態解明を目指すことをゴールとする。
|
| Outline of Final Research Achievements |
At the discovery stage, 300 familial Parkinson's disease (PD) cases, 100 sporadic PD cases, and 200 healthy controls were used to comprehensively analyze 54 lysosomal disease (LSD) genes by targeted sequencing. From the obtained genetic information, we extracted genetic mutations in the familial PD patient group and the sporadic PD patient group, and added statistical analysis with the healthy control group and analysis using the genetic information of the public database. We narrowed down new candidates of causative genes and susceptibility genes. Next, we are going to add gene analyses of the replication stage and isolate novel PD-related genes.
|
| Academic Significance and Societal Importance of the Research Achievements |
新規原因遺伝子候補・感受性遺伝子単離後は、細胞実験・動物実験などの機能解析を進めリソソーム機能障害を治療ターゲットとした創薬を目指すのみならず、リソソーム病のような代謝性疾患ではenzyme replacement therapyが可能でありプレシジョンメディスンの開発を目指すことが可能である。
|
Report
(5 results)
Research Products
(37 results)
-
-
[Journal Article] Investigating the efficacy and safety of elobixibat, an ileal bile acid transporter inhibitor, in patients with Parkinson’s disease with chronic constipation: a multicentre, placebo-controlled, randomised, double-blind, parallel-group study (CONST-PD)2022
Author(s)
Taku Hatano, Genko Oyama, Yasushi Shimo, Kotaro Ogaki, Noriko Nishikawa, Jiro Fukae, Ryota Nakamura, Naohide Kurita, Taiji Tsunemi, Yutaka Oji, Shinji Saiki, Kenya Nishioka, Haruka Takeshige-Amano, et al.
-
Journal Title
BMJ Open
Volume: 12
Issue: 2
Pages: e054129-e054129
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
[Presentation] Detection of genetic modifiers in PRKN,2021
Author(s)
Kotaro Ogaki, Hirofumi Nakaoka, Kensuke Daida, Arisa Hayashid, a, Aya Ikeda, Yuanzhe Li, Hiroyo Yoshino, Manabu Funayama, Kenya Nishioka, Ituro Inoue, Nobutaka Hattori.
Organizer
第14回パーキンソン病・運動障害疾患コングレス 福岡
Related Report
-
[Presentation] Searching for genetic modifiers of PRKN2021
Author(s)
Kotaro Ogaki, Hirofumi Nakaoka, Kensuke Daida, Arisa Hayashid, a, Aya Ikeda, Yuanzhe Li, Hiroyo Yoshino, Manabu Funayama, Kenya Nishioka, Ituro Inoue, Nobutaka Hattori.
Organizer
第62回日本神経学会学術大会
Related Report
-
-
-
[Presentation] Searching for genetic modifiers in PRKN2020
Author(s)
Kotaro Ogaki, Hirofumi Nakaoka, Kensuke Daida, Arisa Hayashida, Aya Ikeda, Yuanzhe Li, Hiroyo Yoshino, Manabu Funayama, Kenya Nishioka, Ituro Inoue, Nobutaka Hattori
Organizer
第61回日本神経学会学術大会
Related Report
-
-
[Presentation] Detection of genetic modifiers in parkin2019
Author(s)
Kotaro Ogaki, Hirofumi Nakaoka, Kensuke Daida, Arisa Hayashida, Aya Ikeda, Yuanzhe Li, Hiroyo Yoshino, Manabu Funayama, Kenya Nishioka, Ituro Inoue, Nobutaka Hattori
Organizer
第60回日本神経学会学術大会
Related Report
-
-
-
-
-
-
-
-
