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LIPAD (LRRK2/Luebeck) International Parkinson’s Disease Study: Protocol and feasibility study

T. Usnich, EJ. Vollstedt, N. Schell, V. Skrahina, X. Bogdanovic, H. Gaber, T. Förster, A. Heuer, N. Koleva-Alazeh, I. Csoti, A. Nazli Basak, S. Ertan, G. Genc, P. Bauer, K. Lohmann, A. Grünewald, E. Schymanski, J. Trinh, S. Schaake, D. Berg, D. Gruber, S. Isaacson, A. Kühn, B. Mollenhauer, D. Pedrosa, K. Reetz, E. Sammler, EM. Valente, F. Valzania, J. Volkmann, S. Zittel, N. Brüggemann, M. Kasten, A. Rolfs, C. Klein (Lübeck, Germany)

Meeting: MDS Virtual Congress 2021

Abstract Number: 762

Keywords: Leucine-rich repeat kinase 2(LRRK2), Parkinson’s

Category: Parkinson's Disease: Genetics

Objective: To systematically assess clinical signs and symptoms including non-motor features, comorbidities, medication and environmental factors in 1,000 participants internationally: 300 with LRRK2 (Leucine-rich repeat kinase 2) -linked Parkinson’s disease (PD), 200 with LRRK2 mutations without PD, 100 PD patients with mutations in GBA or PRKN genes, 200 patients with idiopathic PD, and 200 healthy persons without mutations.

Background: Pathogenic mutations in the LRRK2 gene are the most common known monogenic cause of PD and are inherited in an autosomal-dominant fashion, with reduced, age-dependent penetrance that varies across ethnicities and geographic regions. LRRK2-linked PD is clinically indistinguishable from idiopathic PD. Factors influencing the penetrance of LRRK2 mutations are largely unknown, but represent a therapeutic target in the context of personalized medicine. The international multicenter LIPAD study is a deep-phenotyping follow-up to the Rostock International Parkinson’s Disease Study (ROPAD) that assesses LRRK2 mutations in 10,000 PD patients from 122 sites across Europe, Asia, and the Americas.

Method: Eligible participants are invited for a one-visit personal or online examination using a three-level protocol developed for the LIPAD study 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 for toxicological analyses. Participants with LRRK2 mutations and matched controls are further invited to an on-site visit over two days to participate in an embedded study encompassing multimodal MRI and metabolic studies.

Results: The first ten centers across Germany and five international sites have been initiated, additional centers currently undergo ethical review. The first 100 probands have been enrolled in LIPAD (including 20 online), and seven probands participated in embedded studies (as of February 7th, 2021).

Conclusion: LIPAD is a large-scale international scientific effort focusing on deep phenotyping of LRRK2-linked PD and healthy mutation 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.

To cite this abstract in AMA style:

T. Usnich, EJ. Vollstedt, N. Schell, V. Skrahina, X. Bogdanovic, H. Gaber, T. Förster, A. Heuer, N. Koleva-Alazeh, I. Csoti, A. Nazli Basak, S. Ertan, G. Genc, P. Bauer, K. Lohmann, A. Grünewald, E. Schymanski, J. Trinh, S. Schaake, D. Berg, D. Gruber, S. Isaacson, A. Kühn, B. Mollenhauer, D. Pedrosa, K. Reetz, E. Sammler, EM. Valente, F. Valzania, J. Volkmann, S. Zittel, N. Brüggemann, M. Kasten, A. Rolfs, C. Klein. LIPAD (LRRK2/Luebeck) International Parkinson’s Disease Study: Protocol and feasibility study [abstract]. Mov Disord. 2021; 36 (suppl 1). https://www.mdsabstracts.org/abstract/lipad-lrrk2-luebeck-international-parkinsons-disease-study-protocol-and-feasibility-study/. Accessed May 14, 2025.
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