パーキンソン病のネットワーク進行に対する遺伝子型の影響
In this longitudinal study, the investigators will follow Parkinson's disease (PD) patients with and without glucocerebrosidase (GBA) mutations. The investigators hypothesize that the rate of increase in brain network activity over time (network progression rate) is faster in patients with GBA gene mutations.
調査の概要
状態
条件
詳細な説明
Parkinson's disease (PD) patients with mutations in the glucocerebrosidase gene (GBA) tend to have a more aggressive disease course. GBA may therefore provide a target for disease modifying therapies in mutation carriers. Using positron emission tomography (PET) and magnetic resonance imaging (MRI) brain imaging to measure network progression rates in mutation carriers will allow for the assessment of the potential disease modifying effects of new anti-GBA therapies.
The investigators will also determine whether magnetic resonance imaging (MRI) network methods, which are less invasive and more broadly available than positron emission tomography (PET), produce comparable network progression measurements in individual patients. These determinations will be critical for the design of clinical trials of new disease-modifying drugs.
研究の種類
入学 (実際)
連絡先と場所
研究場所
-
-
New York
-
Manhasset、New York、アメリカ、11030
- Feinstein Institutes for Medical Research
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
Study population will be recruited through local movement disorders centers in the tri-state area, prior PD studies, The Michael J. Fox Trial Finder, community outreach
説明
Inclusion Criteria:
- Diagnosis of PD made according to United Kingdom (UK) Parkinson's Disease Society Brain Bank Criteria
- Ability to provide written informed consent
- Age 40-75
- Stable dose of antiparkinsonian medication for >1 month prior to study entry
Exclusion Criteria:
- Subjects with pathogenic mutations in LRRK2 related PD mutations (subjects with variants of uncertain significance (VUS) are eligible
- History of known causative factors such as encephalitis or neuroleptic treatment
- Patients with dementia (defined as Mini-Mental Status Exam score <24 or a Telephone Interview for Cognitive Status score <26)
- Atypical parkinsonian features including oculomotor abnormalities, incontinence, ataxia, sensory loss, or pyramidal signs
- Known structural brain lesions
- Patients with history of stroke, head injury, high intracranial pressure or severe headaches
- Psychiatric disorder, including a history of major depression in the past 36 months
- Pregnant or breastfeeding women (female subjects of child-bearing potential will be screened for pregnancy before imaging).
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 観測モデル：CASE_CONTROL
- 時間の展望：PROSPECTIVE
コホートと介入
グループ/コホート |
介入・治療 |
|---|---|
|
Parkinson's disease (PD) glucocerebrosidase (GBA) carriers
Parkinson's disease subjects with GBA mutation |
Subjects will be tested for GBA and LRRK2 mutation status at baseline. 18F-Fluoro-2-deoxy-glucose (FDG) PET scan is a nuclear medicine test that measures glucose metabolism (energy) in your brain at baseline and 18 months later. Magnetic Resonance Imaging (MRI) is a noninvasive scan which produces detailed pictures of the brain using a magnetic field. In addition, a special type of MRI, called resting state functional MRI (rs-fMRI), will measure and map brain activity. Conducted at baseline and 18 months later. Investigator will evaluate subjects according to the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the standard clinical tool used to measure the severity and progression of PD. Neuropsychological evaluation will assess how one's brain functions (via pencil and paper testing), which indirectly yields information about the structural and functional integrity of the brain. Conducted at baseline and 18 months later. |
|
Parkinson's disease (PD) non glucocerebrosidase (GBA) carriers
Parkinson's disease subjects without GBA mutation |
Subjects will be tested for GBA and LRRK2 mutation status at baseline. 18F-Fluoro-2-deoxy-glucose (FDG) PET scan is a nuclear medicine test that measures glucose metabolism (energy) in your brain at baseline and 18 months later. Magnetic Resonance Imaging (MRI) is a noninvasive scan which produces detailed pictures of the brain using a magnetic field. In addition, a special type of MRI, called resting state functional MRI (rs-fMRI), will measure and map brain activity. Conducted at baseline and 18 months later. Investigator will evaluate subjects according to the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), the standard clinical tool used to measure the severity and progression of PD. Neuropsychological evaluation will assess how one's brain functions (via pencil and paper testing), which indirectly yields information about the structural and functional integrity of the brain. Conducted at baseline and 18 months later. |
この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Increase in PD related metabolic pattern expression
時間枠：Baseline and 18 months later
|
Changes in PD related and PD cognition related pattern expression in 18F-2-fluoro-2-deoxy-D-glucose (FDG) PET scans |
Baseline and 18 months later
|
|
Increase in PD related functional pattern expression
時間枠：Baseline and 18 months later
|
Changes in PD related and PD cognition related pattern expression in resting state functional magnetic resonance imaging (rs-fMRI) |
Baseline and 18 months later
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Change in motor function
時間枠：Baseline and 18 months later
|
Change in motor function assessed with Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III (The sum score ranges between 0-132 points. Higher scores indicate more severe impairment) |
Baseline and 18 months later
|
|
Change in cognitive function
時間枠：Baseline and 18 months later
|
Change in cognitive function assessed with neuropsychological testing |
Baseline and 18 months later
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：David Eidelberg, MD、Head, Center for Neurosciences
出版物と役立つリンク
一般刊行物
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- Mazzulli JR, Xu YH, Sun Y, Knight AL, McLean PJ, Caldwell GA, Sidransky E, Grabowski GA, Krainc D. Gaucher disease glucocerebrosidase and alpha-synuclein form a bidirectional pathogenic loop in synucleinopathies. Cell. 2011 Jul 8;146(1):37-52. doi: 10.1016/j.cell.2011.06.001. Epub 2011 Jun 23.
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- Winder-Rhodes SE, Evans JR, Ban M, Mason SL, Williams-Gray CH, Foltynie T, Duran R, Mencacci NE, Sawcer SJ, Barker RA. Glucocerebrosidase mutations influence the natural history of Parkinson's disease in a community-based incident cohort. Brain. 2013 Feb;136(Pt 2):392-9. doi: 10.1093/brain/aws318.
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- Sidransky E, Lopez G. The link between the GBA gene and parkinsonism. Lancet Neurol. 2012 Nov;11(11):986-98. doi: 10.1016/S1474-4422(12)70190-4.
- Schindlbeck KA, Eidelberg D. Network imaging biomarkers: insights and clinical applications in Parkinson's disease. Lancet Neurol. 2018 Jul;17(7):629-640. doi: 10.1016/S1474-4422(18)30169-8.
- Alcalay RN, Levy OA, Waters CC, Fahn S, Ford B, Kuo SH, Mazzoni P, Pauciulo MW, Nichols WC, Gan-Or Z, Rouleau GA, Chung WK, Wolf P, Oliva P, Keutzer J, Marder K, Zhang X. Glucocerebrosidase activity in Parkinson's disease with and without GBA mutations. Brain. 2015 Sep;138(Pt 9):2648-58. doi: 10.1093/brain/awv179. Epub 2015 Jun 27.
- Niethammer M, Eidelberg D. Metabolic brain networks in translational neurology: concepts and applications. Ann Neurol. 2012 Nov;72(5):635-47. doi: 10.1002/ana.23631. Epub 2012 Aug 31.
- Eidelberg D. Metabolic brain networks in neurodegenerative disorders: a functional imaging approach. Trends Neurosci. 2009 Oct;32(10):548-57. doi: 10.1016/j.tins.2009.06.003. Epub 2009 Sep 16.
- Vo A, Sako W, Fujita K, Peng S, Mattis PJ, Skidmore FM, Ma Y, Ulug AM, Eidelberg D. Parkinson's disease-related network topographies characterized with resting state functional MRI. Hum Brain Mapp. 2017 Feb;38(2):617-630. doi: 10.1002/hbm.23260. Epub 2016 May 21.
- Schindlbeck, K.A. et al., Multicenter validation of disease-related Parkinson's disease pattern with resting state fMRI. 21st International Congress of Parkinson's Disease and Movement Disorders, June 8, 2018, Vancouver, Canada
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- Niethammer M, Tang CC, LeWitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW, Eskandar EN, Kostyk SK, Sarkar A, Siddiqui MS, Tatter SB, Schwalb JM, Poston KL, Henderson JM, Kurlan RM, Richard IH, Sapan CV, Eidelberg D, During MJ, Kaplitt MG, Feigin A. Long-term follow-up of a randomized AAV2-GAD gene therapy trial for Parkinson's disease. JCI Insight. 2017 Apr 6;2(7):e90133. doi: 10.1172/jci.insight.90133.
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研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
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その他の研究ID番号
- MJFF grant 16325
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