Peripheral blood transcriptome profiling enables monitoring disease progression in dystrophic mice and patients
Abstract 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 mus...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2021-04-01
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| Series: | EMBO Molecular Medicine |
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| Online Access: | https://doi.org/10.15252/emmm.202013328 |
| _version_ | 1797283269655396352 |
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| author | Mirko Signorelli Mitra Ebrahimpoor Olga Veth Kristina Hettne Nisha Verwey Raquel García‐Rodríguez Christa L Tanganyika‐deWinter Luz B Lopez Hernandez Rosa Escobar Cedillo Benjamín Gómez Díaz Olafur T Magnusson Hailiang Mei Roula Tsonaka Annemieke Aartsma‐Rus Pietro Spitali |
| author_facet | Mirko Signorelli Mitra Ebrahimpoor Olga Veth Kristina Hettne Nisha Verwey Raquel García‐Rodríguez Christa L Tanganyika‐deWinter Luz B Lopez Hernandez Rosa Escobar Cedillo Benjamín Gómez Díaz Olafur T Magnusson Hailiang Mei Roula Tsonaka Annemieke Aartsma‐Rus Pietro Spitali |
| author_sort | Mirko Signorelli |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-07T17:28:37Z |
| format | Article |
| id | doaj.art-ece83370f1b449858b7ecf64cf32618c |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2024-03-07T17:28:37Z |
| publishDate | 2021-04-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-ece83370f1b449858b7ecf64cf32618c2024-03-02T18:34:51ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842021-04-01134n/an/a10.15252/emmm.202013328Peripheral blood transcriptome profiling enables monitoring disease progression in dystrophic mice and patientsMirko Signorelli0Mitra Ebrahimpoor1Olga Veth2Kristina Hettne3Nisha Verwey4Raquel García‐Rodríguez5Christa L Tanganyika‐deWinter6Luz B Lopez Hernandez7Rosa Escobar Cedillo8Benjamín Gómez Díaz9Olafur T Magnusson10Hailiang Mei11Roula Tsonaka12Annemieke Aartsma‐Rus13Pietro Spitali14Department of Biomedical Data Sciences Leiden University Medical Center Leiden The NetherlandsDepartment of Biomedical Data Sciences Leiden University Medical Center Leiden The NetherlandsDepartment of Human Genetics Leiden University Medical Center Leiden The NetherlandsDepartment of Human Genetics Leiden University Medical Center Leiden The NetherlandsDepartment of Human Genetics Leiden University Medical Center Leiden The NetherlandsDepartment of Human Genetics Leiden University Medical Center Leiden The NetherlandsDepartment of Human Genetics Leiden University Medical Center Leiden The NetherlandsDepartamento de Medicina Genómica Universidad Autónoma de Guadalajara Guadalajara MexicoSociedad Mexicana de la Distrofia Muscular A.C INR‐LGII Ciudad de México MexicoSociedad Mexicana de la Distrofia Muscular A.C INR‐LGII Ciudad de México MexicodeCODE genetics/Amgen Reykjavik IcelandSequencing Analysis Support Core Leiden University Medical Center Leiden The NetherlandsDepartment of Biomedical Data Sciences Leiden University Medical Center Leiden The NetherlandsDepartment of Human Genetics Leiden University Medical Center Leiden The NetherlandsDepartment of Human Genetics Leiden University Medical Center Leiden The NetherlandsAbstract 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.https://doi.org/10.15252/emmm.202013328biomarkersDuchenne muscular dystrophydystrophinopathiesRNA‐seq |
| spellingShingle | Mirko Signorelli Mitra Ebrahimpoor Olga Veth Kristina Hettne Nisha Verwey Raquel García‐Rodríguez Christa L Tanganyika‐deWinter Luz B Lopez Hernandez Rosa Escobar Cedillo Benjamín Gómez Díaz Olafur T Magnusson Hailiang Mei Roula Tsonaka Annemieke Aartsma‐Rus Pietro Spitali Peripheral blood transcriptome profiling enables monitoring disease progression in dystrophic mice and patients EMBO Molecular Medicine biomarkers Duchenne muscular dystrophy dystrophinopathies RNA‐seq |
| title | Peripheral blood transcriptome profiling enables monitoring disease progression in dystrophic mice and patients |
| title_full | Peripheral blood transcriptome profiling enables monitoring disease progression in dystrophic mice and patients |
| title_fullStr | Peripheral blood transcriptome profiling enables monitoring disease progression in dystrophic mice and patients |
| title_full_unstemmed | Peripheral blood transcriptome profiling enables monitoring disease progression in dystrophic mice and patients |
| title_short | Peripheral blood transcriptome profiling enables monitoring disease progression in dystrophic mice and patients |
| title_sort | peripheral blood transcriptome profiling enables monitoring disease progression in dystrophic mice and patients |
| topic | biomarkers Duchenne muscular dystrophy dystrophinopathies RNA‐seq |
| url | https://doi.org/10.15252/emmm.202013328 |
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