Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson’s disease

Sara Gomes; Alicia  Garrido; Francesca Tonelli; Donina Obiang; Eduardo  Tolosa; Maria  José Martí; Javier Ruiz-Martínez; Ana  Vinagre Aragón; Haizea Hernandez-Eguiazu; Ioana  Croitoru; Vicky L. Marshall; Theresa Koenig; Christoph  Hotzy; Frank Hsieh; Marianna Sakalosh; Elizabeth Tengstrand; Shalini Padmanabhan; Kalpana M. Merchant; Christof Bruecke; Walter Pirker; Alexander  Zimprich; Esther Sammler

doi:10.1038/s41531-023-00482-4

Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson’s disease

Sara Gomes
, Alicia Garrido
, Francesca Tonelli
, Donina Obiang
, Eduardo Tolosa
, Maria José Martí
, Javier Ruiz-Martínez
, Ana Vinagre Aragón
, Haizea Hernandez-Eguiazu
, Ioana Croitoru
, Vicky L. Marshall
, Theresa Koenig
, Christoph Hotzy
, Frank Hsieh
, Marianna Sakalosh
, Elizabeth Tengstrand
, Shalini Padmanabhan
, Kalpana M. Merchant
, Christof Bruecke
, Walter Pirker

Alexander Zimprich, Esther Sammler (Lead / Corresponding author)

MRC PPU

Research output: Contribution to journal › Article › peer-review

26 Citations (Scopus)

257 Downloads (Pure)

Abstract

Elevated urine bis(monoacylglycerol)phosphate (BMP) levels have been found in gain-of-kinase function LRRK2 G2019S mutation carriers. Here, we have expanded urine BMP analysis to other Parkinson’s disease (PD) associated mutations and found them to be consistently elevated in carriers of LRRK2 G2019S and R1441G/C as well as VPS35 D620N mutations. Urine BMP levels are promising biomarkers for patient stratification and potentially target engagement in clinical trials of emerging targeted PD therapies.

Original language	English
Article number	52
Number of pages	4
Journal	NPJ Parkinson's disease
Volume	9
DOIs	https://doi.org/10.1038/s41531-023-00482-4
Publication status	Published - 4 Apr 2023

Keywords

Parkinson's disease
Translational research

ASJC Scopus subject areas

Clinical Neurology
Neurology
Cellular and Molecular Neuroscience

Access to Document

10.1038/s41531-023-00482-4Licence: CC BY

Final Published VersionFinal published version, 778 KBLicence: CC BY

Cite this

Gomes, S., Garrido, A., Tonelli, F., Obiang, D., Tolosa, E., José Martí, M., Ruiz-Martínez, J., Vinagre Aragón, A., Hernandez-Eguiazu, H., Croitoru, I., Marshall, V. L., Koenig, T., Hotzy, C., Hsieh, F., Sakalosh, M., Tengstrand, E., Padmanabhan, S., Merchant, K. M., Bruecke, C., ... Sammler, E. (2023). Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson’s disease. NPJ Parkinson's disease, 9, Article 52. https://doi.org/10.1038/s41531-023-00482-4

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title = "Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson{\textquoteright}s disease",

abstract = "Elevated urine bis(monoacylglycerol)phosphate (BMP) levels have been found in gain-of-kinase function LRRK2 G2019S mutation carriers. Here, we have expanded urine BMP analysis to other Parkinson{\textquoteright}s disease (PD) associated mutations and found them to be consistently elevated in carriers of LRRK2 G2019S and R1441G/C as well as VPS35 D620N mutations. Urine BMP levels are promising biomarkers for patient stratification and potentially target engagement in clinical trials of emerging targeted PD therapies.",

keywords = "Parkinson's disease, Translational research",

author = "Sara Gomes and Alicia Garrido and Francesca Tonelli and Donina Obiang and Eduardo Tolosa and \{Jos{\'e} Mart{\'i}\}, Maria and Javier Ruiz-Mart{\'i}nez and \{Vinagre Arag{\'o}n\}, Ana and Haizea Hernandez-Eguiazu and Ioana Croitoru and Marshall, \{Vicky L.\} and Theresa Koenig and Christoph Hotzy and Frank Hsieh and Marianna Sakalosh and Elizabeth Tengstrand and Shalini Padmanabhan and Merchant, \{Kalpana M.\} and Christof Bruecke and Walter Pirker and Alexander Zimprich and Esther Sammler",

note = "Funding Information: The work was supported by funding from the Michael J. Fox Foundation for Parkinson{\textquoteright}s Research [MJFF-020316, MJFF-009262]. E.S. was supported by a Chief Scientist Office Scottish Senior Clinical Academic Fellowship. We thank all patients and volunteers who have participated in this study. We acknowledge the excellent technical support of the MRC-Protein Phosphorylation and Ubiquitylation Unit (PPU) and MRC PPU Reagents and Services teams. We thank the Data Analysis Group at the School of Life Sciences at the University of Dundee for their useful discussion and guidance. Copyright: {\textcopyright} 2023, The Author(s).",

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doi = "10.1038/s41531-023-00482-4",

language = "English",

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Gomes, S, Garrido, A, Tonelli, F, Obiang, D, Tolosa, E, José Martí, M, Ruiz-Martínez, J, Vinagre Aragón, A, Hernandez-Eguiazu, H, Croitoru, I, Marshall, VL, Koenig, T, Hotzy, C, Hsieh, F, Sakalosh, M, Tengstrand, E, Padmanabhan, S, Merchant, KM, Bruecke, C, Pirker, W, Zimprich, A & Sammler, E 2023, 'Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson’s disease', NPJ Parkinson's disease, vol. 9, 52. https://doi.org/10.1038/s41531-023-00482-4

TY - JOUR

T1 - Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson’s disease

AU - Gomes, Sara

AU - Garrido, Alicia

AU - Tonelli, Francesca

AU - Obiang, Donina

AU - Tolosa, Eduardo

AU - José Martí, Maria

AU - Ruiz-Martínez, Javier

AU - Vinagre Aragón, Ana

AU - Hernandez-Eguiazu, Haizea

AU - Croitoru, Ioana

AU - Marshall, Vicky L.

AU - Koenig, Theresa

AU - Hotzy, Christoph

AU - Hsieh, Frank

AU - Sakalosh, Marianna

AU - Tengstrand, Elizabeth

AU - Padmanabhan, Shalini

AU - Merchant, Kalpana M.

AU - Bruecke, Christof

AU - Pirker, Walter

AU - Zimprich, Alexander

AU - Sammler, Esther

N1 - Funding Information: The work was supported by funding from the Michael J. Fox Foundation for Parkinson’s Research [MJFF-020316, MJFF-009262]. E.S. was supported by a Chief Scientist Office Scottish Senior Clinical Academic Fellowship. We thank all patients and volunteers who have participated in this study. We acknowledge the excellent technical support of the MRC-Protein Phosphorylation and Ubiquitylation Unit (PPU) and MRC PPU Reagents and Services teams. We thank the Data Analysis Group at the School of Life Sciences at the University of Dundee for their useful discussion and guidance. Copyright: © 2023, The Author(s).

PY - 2023/4/4

Y1 - 2023/4/4

N2 - Elevated urine bis(monoacylglycerol)phosphate (BMP) levels have been found in gain-of-kinase function LRRK2 G2019S mutation carriers. Here, we have expanded urine BMP analysis to other Parkinson’s disease (PD) associated mutations and found them to be consistently elevated in carriers of LRRK2 G2019S and R1441G/C as well as VPS35 D620N mutations. Urine BMP levels are promising biomarkers for patient stratification and potentially target engagement in clinical trials of emerging targeted PD therapies.

AB - Elevated urine bis(monoacylglycerol)phosphate (BMP) levels have been found in gain-of-kinase function LRRK2 G2019S mutation carriers. Here, we have expanded urine BMP analysis to other Parkinson’s disease (PD) associated mutations and found them to be consistently elevated in carriers of LRRK2 G2019S and R1441G/C as well as VPS35 D620N mutations. Urine BMP levels are promising biomarkers for patient stratification and potentially target engagement in clinical trials of emerging targeted PD therapies.

KW - Parkinson's disease

KW - Translational research

UR - https://www.scopus.com/pages/publications/85152696463

U2 - 10.1038/s41531-023-00482-4

DO - 10.1038/s41531-023-00482-4

M3 - Article

C2 - 37015928

SN - 2373-8057

VL - 9

JO - NPJ Parkinson's disease

JF - NPJ Parkinson's disease

M1 - 52

ER -

Elevated urine BMP phospholipids in LRRK2 and VPS35 mutation carriers with and without Parkinson’s disease

Abstract

Keywords

ASJC Scopus subject areas

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Differential LRRK2 Dependent Rab Phosphorylation Signatures in Peripheral Blood and Urine in Idiopathic and Monogenetic PD

Bench-to-Bedside Parkinson's Disease Research: Biomarkers in LRRK2 (NHS Research Scotland (NRS) and Scottish Universities Scottish Senior Clinical Academic Fellowship Scheme)