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Longitudinal serum ...
Longitudinal serum biomarker screening identifies malate dehydrogenase 2 as candidate prognostic biomarker for Duchenne muscular dystrophy
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- Signorelli, Mirko (författare)
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
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- Ayoglu, Burcu (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Cellulär och klinisk proteomik
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- Johansson, Camilla (författare)
- KTH,Systembiologi
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- Lockmüller, Hanns (författare)
- Department of Neuropediatrics and Muscle Disorders, Faculty of Medicine, Medical Center, University of Freiburg, Freiburg, Germany
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- Straub, Volker (författare)
- MRC Centre for Neuromuscular Diseases, Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne, UK
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- Muntoni, Francesco (författare)
- The Dubowitz Neuromuscular Centre, UCL Institute of Child Health, London, UK
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- Niks, Erik H. (författare)
- Department of Neurology, Leiden University Medical Center, Leiden, The Netherlands
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- Tsonaka, Roula (författare)
- Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands
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- Aartsma-Rus, Annemieke (författare)
- Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
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- Nilsson, Peter (författare)
- KTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik
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- Al-Khalili Szigyarto, Cristina (författare)
- KTH,Skolan för kemi, bioteknologi och hälsa (CBH)
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- Spitali, Pietro (författare)
- Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands
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(creator_code:org_t)
- Wiley, 2020
- 2020
- Engelska.
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Ingår i: Journal of Cachexia, Sarcopenia and Muscle. - : Wiley. - 2190-5991 .- 2190-6009. ; 11:2, s. 505-517
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https://doi.org/10.1...
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https://kth.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- AbstractBackgroundDuchenne muscular dystrophy (DMD) is a fatal disease for which no cure is available. Clinical trials have shown to be largely underpowered due to inter‐individual variability and noisy outcome measures. The availability of biomarkers able to anticipate clinical benefit is highly needed to improve clinical trial design and facilitate drug development.MethodsIn this study, we aimed to appraise the value of protein biomarkers to predict prognosis and monitor disease progression or treatment outcome in patients affected by DMD. We collected clinical data and 303 blood samples from 157 DMD patients in three clinical centres; 78 patients contributed multiple blood samples over time, with a median follow‐up time of 2 years. We employed linear mixed models to identify biomarkers that are associated with disease progression, wheelchair dependency, and treatment with corticosteroids and performed survival analysis to find biomarkers whose levels are associated with time to loss of ambulation.ResultsOur analysis led to the identification of 21 proteins whose levels significantly decrease with age and nine proteins whose levels significantly increase. Seven of these proteins are also differentially expressed in non‐ambulant patients, and three proteins are differentially expressed in patients treated with glucocorticosteroids. Treatment with corticosteroids was found to partly counteract the effect of disease progression on two biomarkers, namely, malate dehydrogenase 2 (MDH2, P = 0.0003) and ankyrin repeat domain 2 (P = 0.0005); however, patients treated with corticosteroids experienced a further reduction on collagen 1 serum levels (P = 0.0003), especially following administration of deflazacort. A time to event analysis allowed to further support the use of MDH2 as a prognostic biomarker as it was associated with an increased risk of wheelchair dependence (P = 0.0003). The obtained data support the prospective evaluation of the identified biomarkers in natural history and clinical trials as exploratory biomarkers.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Nyckelord
- Duchenne muscular dystrophy
- Protein biomarkers
- Prognostic biomarker
- Rare diseases
- Serum biomarkers
- Biotechnology
- Bioteknologi
Publikations- och innehållstyp
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- art (ämneskategori)
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- Av författaren/redakt...
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Signorelli, Mirk ...
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Ayoglu, Burcu
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Johansson, Camil ...
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Lockmüller, Hann ...
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Straub, Volker
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Muntoni, Frances ...
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visa fler...
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Niks, Erik H.
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Tsonaka, Roula
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Aartsma-Rus, Ann ...
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Nilsson, Peter
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Al-Khalili Szigy ...
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Spitali, Pietro
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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