Peripheral blood transcriptome profiling enables monitoring disease progression in dystrophic mice and patients
| Autor: | Olafur T. Magnusson, Olga Veth, Mitra Ebrahimpoor, Mirko Signorelli, Luz B Lopez Hernandez, Christa L Tanganyika-deWinter, Kristina Hettne, Nisha Verwey, Annemieke Aartsma-Rus, Roula Tsonaka, Pietro Spitali, Benjamín Gómez Díaz, Hailiang Mei, Raquel García-Rodríguez, Rosa Escobar Cedillo |
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| Rok vydání: | 2021 |
| Předmět: |
Duchenne muscular dystrophy
0301 basic medicine Oncology Medicine (General) medicine.medical_specialty QH426-470 Article Mice 03 medical and health sciences R5-920 0302 clinical medicine Internal medicine Gene expression Genetics Animals Humans Medicine Muscle Skeletal Musculoskeletal System Biomarkers & Diagnostic Imaging biology business.industry Gene Expression Profiling biomarkers Skeletal muscle Articles medicine.disease Pathophysiology Pre-clinical development Muscular Dystrophy Duchenne Clinical trial 030104 developmental biology medicine.anatomical_structure Cohort Disease Progression Mice Inbred mdx biology.protein RNA‐seq Molecular Medicine dystrophinopathies Transcriptome business Dystrophin 030217 neurology & neurosurgery |
| Zdroj: | EMBO Molecular Medicine EMBO Molecular Medicine, 13(4). WILEY EMBO Molecular Medicine, Vol 13, Iss 4, Pp n/a-n/a (2021) |
| ISSN: | 1757-4684 1757-4676 |
| DOI: | 10.15252/emmm.202013328 |
| Popis: | DMD is a rare disorder characterized by progressive muscle degeneration and premature death. Therapy development is delayed by difficulties to monitor efficacy non‐invasively in clinical trials. In this study, we used RNA‐sequencing to describe the pathophysiological changes in skeletal muscle of 3 dystrophic mouse models. We show how dystrophic changes in muscle are reflected in blood by analyzing paired muscle and blood samples. Analysis of repeated blood measurements followed the dystrophic signature at five equally spaced time points over a period of seven months. Treatment with two antisense drugs harboring different levels of dystrophin recovery identified genes associated with safety and efficacy. Evaluation of the blood gene expression in a cohort of DMD patients enabled the comparison between preclinical models and patients, and the identification of genes associated with physical performance, treatment with corticosteroids and body measures. The presented results provide evidence that blood RNA‐sequencing can serve as a tool to evaluate disease progression in dystrophic mice and patients, as well as to monitor response to (dystrophin‐restoring) therapies in preclinical drug development and in clinical trials. This study explored the potential of RNA‐sequencing of peripheral blood to track non‐invasively disease progression and response to treatment in dystrophic mice and in patients affected by Duchenne Muscular Dystrophy (DMD). |
| Databáze: | OpenAIRE |
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