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| 1 | Prodromal Parkinson’s disease: hype or hope for disease-modification trials?显示文摘The ultimate goal in Parkinson’s disease (PD) research remains the identification of treatments that are capable of slowing or even halting the progression of the disease. The failure of numerous past disease-modification trials in PD has been attributed to a variety of factors related not only to choosing wrong interventions, but also to using inadequate trial designs and target populations. In patients with clinically established PD, neuronal pathology may already have advanced too far to be modified by any intervention. Based on such reasoning, individuals in yet prediagnostic or prodromal disease stages, may provide a window of opportunity to test disease-modifying strategies. There is now sufficient evidence from prospective studies to define diagnostic criteria for prodromal PD and several approaches have been studied in observational cohorts. These include the use of PD-risk algorithms derived from multiple established risk factors for disease as well as follow-up of cohorts with single defined prodromal markers like hyposmia, rapid eye movement sleep behavior disorders, or PD gene carriers. In this review, we discuss recruitment strategies for disease-modification trials in various prodromal PD cohorts, as well as potential trial designs, required trial durations, and estimated sample sizes. We offer a concluding outlook on how the goal of implementing disease-modification trials in prodromal cohorts might be achieved in the future. | Philipp Mahlknecht Kathrin Marini Mario Werkmann Werner Poewe Klaus Seppi | 2022 | Translational Neurodegeneration2022，11，1： | 2 |
| 2 | Azacytidine causes complex DNA methylation responses in myeloid leukemia显示文摘 | Stresemann C Bokelmann I Mahlknecht U | 2008 | Mol Cancer Ther2008，7，9： | 1 |
| 3 | Inhibition of pancreatic carcinoma by homo- and heterocombinations of antibodies against EGF-receptor and its kin HER2/ErbB-2显示文摘 | Ruth Maron Bilha Schechter Maicol Mancini Georg Mahlknecht Yosef Yarden Michael Sela | 2013 | Proceedings of the National Academy of Sciences2013，，38： | 1 |
| 4 | Groundwater recharge in a sedimentary basin in semi-arid Mexico显示文摘 | Mahlknecht J Schneider J F Merkel B J | 2004 | Hydrogeology Journal2004，12，5： | 1 |
| 5 | Valproic acid and all-trans retinoic acid: meta-analysis of a palliative treatment regimen in AML and MDS patients显示文摘 | Bellos F Mahlknecht U | 2008 | Onkologie2008，31，11： | 1 |
| 6 | A real-time image recognition systemfor tiny autonomous mobile robots显示文摘 | MAHLKNECHT Stefan OBERHAMMER Roland NO-VAK Gregor | 2005 | Real-Time Sys-tems2005，29，23： | 1 |
| 7 | The histone deacetylase inhibitor suberoylanilide hydroxamic acid down-regulates expression levels of Bcr-abl,c-Myc and HD AC3 in chronic myeloid leukemia cell lines显示文摘 | Xu Y Voelter-Mahlknecht S Mahlknecht U | 2005 | Int J Mol Med2005，15，1： | 1 |
| 8 | SIRTUIN 1: regulating the regulator显示文摘 | Zschoernig B Mahlknecht U | 2008 | Biochem Biophys Res Commun2008，376，2： | 1 |
| 9 | Role of histone deacetylase inhibitors in the treatment of cancer显示文摘 | Mei S Ho A D Mahlknecht U | 2004 | Int J Oncol2004，25，6： | 1 |
| 10 | Therapeutic advances in multiple system atrophy and progressive supranuclear palsy显示文摘 | Poewe W Mahlknecht P Krismer F | 2015 | Mov Disord2015，，： | 1 |
| 11 | Groundwater chemistry and mass transfers in the Independence aquifer, central Mexico, by using multivariate statistics and mass-balance models显示文摘 | MAHLKNECHT J STEINICH B NavaRro I | 2004 | Environmental Geology2004，45，： | 1 |
| 12 | The histone deacetylase inhibitor suberoylanilide hydroxamic acid down-regulates expression levels of Bcr-abl,c-Myc and HDAC3 in chronic myeloid leukemia cell lines显示文摘 | Xu Y Voelter-Mahlknecht S Mahlknecht U | 2005 | Int J Mol Med2005，15，1： | 1 |
| 13 | Histone deacetylase inhibitor treat-ment downregulates VLA-4 adhesion in hematopoietic stem cellsand acute myeloid leukemia blast cells显示文摘 | Mahlknecht U Schonbein C | 2008 | Haematologica2008，93，3： | 1 |
| 14 | Groundwater recharge in a sedimentary basin in semi-arid 显示文摘 | Mahlknecht J Schneider J F Merkel B J | 2004 | Mexico Hydrogeology Journal2004，12，： | 1 |
| 15 | Groundwater recharge in a sedimentary basin in semi-arid Mexico 显示文摘 | Mahlknecht J Schneider J F Merkel B J | 2004 | Hydrogeology Journal2004，12，： | 1 |
| 16 | Valproic acid sensitizes chronic lymphocytic leukemia cells to apoptosis and restores the balance between pro-and antiapoptotic proteins显示文摘 | Bokelmann I Mahlknecht U | 2008 | Mol Med2008，14，12： | 1 |
| 17 | Aptamer to ErbB-2/HER2 enhances degradation of the target and inhibits tu- morigenic growth 显示文摘 | MAHLKNECHT G MARON R MANCINI M | 2013 | Proc Natl Acad Sci USA2013，110，20： | 1 |
| 18 | Stem cells and aging显示文摘 | Anthony DH Wolfgang Wagner Ulrich Mahlknecht | 2005 | EMBO Reports2005，6，1： | 1 |
| 19 | The histone deace-tylase inhibitor suberoylanilide hydroxamic acid down-regulates expression levels of Bcr-abl,c-Myc and HDAC3 in chronic myeloid leukemia cell lines显示文摘 | Xu Y Voelter-Mahlknecht S Mahlknecht U | 2005 | Int J Mol Med2005，15，1： | 1 |
| 20 | Aptamer to ErbB-2/HER2 enhances degradation of the target and inhibits tumorigenic growth显示文摘 | Mahlknecht G Maron R Mancini M | 2013 | Proc Natl Acad Sci USA2013，110，20： | 1 |
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