TY - JOUR
T1 - LIPAD (LRRK2/Luebeck International Parkinson's Disease) Study Protocol
T2 - Deep Phenotyping of an International Genetic Cohort
AU - Usnich, Tatiana
AU - Vollstedt, Eva-Juliane
AU - Schell, Nathalie
AU - Skrahina, Volha
AU - Bogdanovic, Xenia
AU - Gaber, Hanaa
AU - Förster, Toni M.
AU - Heuer, Andreas
AU - Koleva-Alazeh, Natalia
AU - Csoti, Ilona
AU - Basak, Ayse Nazli
AU - Ertan, Sibel
AU - Genc, Gencer
AU - Bauer, Peter
AU - Lohmann, Katja
AU - Grünewald, Anne
AU - Schymanski, Emma L.
AU - Trinh, Joanne
AU - Schaake, Susen
AU - Berg, Daniela
AU - Gruber, Doreen
AU - Isaacson, Stuart H.
AU - Kühn, Andrea A.
AU - Mollenhauer, Brit
AU - Pedrosa, David J.
AU - Reetz, Kathrin
AU - Sammler, Esther M.
AU - Valente, Enza Maria
AU - Valzania, Franco
AU - Volkmann, Jens
AU - Zittel, Simone
AU - Brüggemann, Norbert
AU - Kasten, Meike
AU - Rolfs, Arndt
AU - Klein, Christine
N1 - The LIPAD study has been supported by institutional funds (Institute of Neurogenetics, University of Lübeck), and partly supported by Centogene GmbH. AB (NDAL) was funded by Suna and Inan Kirac Foundation, grant no 2018-2020. ESc was supported by the Luxembourg National Research Fund (FNR) for project A18/BM/12341006.
Copyright © 2021 Usnich, Vollstedt, Schell, Skrahina, Bogdanovic, Gaber, Förster, Heuer, Koleva-Alazeh, Csoti, Basak, Ertan, Genc, Bauer, Lohmann, Grünewald, Schymanski, Trinh, Schaake, Berg, Gruber, Isaacson, Kühn, Mollenhauer, Pedrosa, Reetz, Sammler, Valente, Valzania, Volkmann, Zittel, Brüggemann, Kasten, Rolfs, Klein and The LIPAD Study Group.
PY - 2021/8/9
Y1 - 2021/8/9
N2 - Background: Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most common known monogenic cause of Parkinson's disease (PD). LRRK2-linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced penetrance and variable expressivity that differ across ethnicities and geographic regions.Objective: To systematically assess clinical signs and symptoms including non-motor features, comorbidities, medication and environmental factors in PD patients, unaffected LRRK2 pathogenic variant carriers, and controls. A further focus is to enable the investigation of modifiers of penetrance and expressivity of LRRK2 pathogenic variants using genetic and environmental data.Methods: Eligible participants are invited for a personal or online examination which comprises completion of a detailed eCRF and collection of blood samples (to obtain DNA, RNA, serum/plasma, immune cells), urine as well as household dust. We plan to enroll 1,000 participants internationally: 300 with LRRK2-linked PD, 200 with LRRK2 pathogenic variants but without PD, 100 PD patients with pathogenic variants in the GBA or PRKN genes, 200 patients with idiopathic PD, and 200 healthy persons without pathogenic variants.Results: The eCRF consists of an investigator-rated (1 h) and a self-rated (1.5 h) part. The first part includes the Movement Disorder Society Unified Parkinson's Disease Rating, Hoehn &Yahr, and Schwab & England Scales, the Brief Smell Identification Test, and Montreal Cognitive Assessment. The self-rating part consists of a PD risk factor, food frequency, autonomic dysfunction, and quality of life questionnaires, the Pittsburgh Sleep Quality Inventory, and the Epworth Sleepiness as well as the Hospital Anxiety and Depression Scales. The first 15 centers have been initiated and the first 150 participants enrolled (as of March 25th, 2021).Conclusions: LIPAD is a large-scale international scientific effort focusing on deep phenotyping of LRRK2-linked PD and healthy pathogenic variant carriers, including the comparison with additional relatively frequent genetic forms of PD, with a future perspective to identify genetic and environmental modifiers of penetrance and expressivity.Clinical Trial Registration: ClinicalTrials.gov, NCT04214509.
AB - Background: Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most common known monogenic cause of Parkinson's disease (PD). LRRK2-linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced penetrance and variable expressivity that differ across ethnicities and geographic regions.Objective: To systematically assess clinical signs and symptoms including non-motor features, comorbidities, medication and environmental factors in PD patients, unaffected LRRK2 pathogenic variant carriers, and controls. A further focus is to enable the investigation of modifiers of penetrance and expressivity of LRRK2 pathogenic variants using genetic and environmental data.Methods: Eligible participants are invited for a personal or online examination which comprises completion of a detailed eCRF and collection of blood samples (to obtain DNA, RNA, serum/plasma, immune cells), urine as well as household dust. We plan to enroll 1,000 participants internationally: 300 with LRRK2-linked PD, 200 with LRRK2 pathogenic variants but without PD, 100 PD patients with pathogenic variants in the GBA or PRKN genes, 200 patients with idiopathic PD, and 200 healthy persons without pathogenic variants.Results: The eCRF consists of an investigator-rated (1 h) and a self-rated (1.5 h) part. The first part includes the Movement Disorder Society Unified Parkinson's Disease Rating, Hoehn &Yahr, and Schwab & England Scales, the Brief Smell Identification Test, and Montreal Cognitive Assessment. The self-rating part consists of a PD risk factor, food frequency, autonomic dysfunction, and quality of life questionnaires, the Pittsburgh Sleep Quality Inventory, and the Epworth Sleepiness as well as the Hospital Anxiety and Depression Scales. The first 15 centers have been initiated and the first 150 participants enrolled (as of March 25th, 2021).Conclusions: LIPAD is a large-scale international scientific effort focusing on deep phenotyping of LRRK2-linked PD and healthy pathogenic variant carriers, including the comparison with additional relatively frequent genetic forms of PD, with a future perspective to identify genetic and environmental modifiers of penetrance and expressivity.Clinical Trial Registration: ClinicalTrials.gov, NCT04214509.
KW - GBA
KW - LRRK2
KW - Parkinson's disease
KW - clinical study
KW - genetic cohort
UR - http://www.scopus.com/inward/record.url?scp=85114226575&partnerID=8YFLogxK
U2 - 10.3389/fneur.2021.710572
DO - 10.3389/fneur.2021.710572
M3 - Article
C2 - 34475849
SN - 1664-2295
VL - 12
JO - Frontiers in Neurology
JF - Frontiers in Neurology
M1 - 710572
ER -