Predictors of participation restriction over a 9-year period in adults with myotonic dystrophy type 1

Raymond, Kateri; Levasseur, Mélanie; Gallais, Benjamin; Richer, Louis; Laberge, Luc; Petitclerc, Émilie; Mathieu, Jean; Gagnon, Cynthia

doi:10.1080/09638288.2020.1837264

Cited by 7 publications

(10 citation statements)

References 79 publications

(102 reference statements)

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“…Muscle strength was expressed as the expected muscle strength of healthy individuals based on a French isometric strength normative database using predictive equations taking into consideration age, sex, and weight of the patients 31 . Patients were subjected to a battery of validated functional tests 63, 64 . Timed-up and Go: time to stand up, walk three meters, turn and walk back to sit down on the chair; 10mWT: comfortable walking speed (m/s) along a 10-meter distance; Berg balance scale: 14 items measuring static and dynamic balance (maximum score of 56 indicating no deficit in balance); Pinch strength: measured using a B&L pinch gauge (kg).…”

Section: Methodsmentioning

confidence: 99%

Clearance of defective muscle stem cells by senolytics reduces the expression of senescence-associated secretory phenotype and restores myogenesis in myotonic dystrophy type 1

Conte

Bishop

Orfi

et al. 2022

Preprint

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Muscle weakness and atrophy are clinical hallmarks of myotonic dystrophy type 1 (DM1). Muscle stem cells, which contribute to skeletal muscle growth and repair, are also affected in this disease. However, the molecular mechanisms leading to this defective activity and the impact on the disease severity are still elusive. Here, we explored through an unbiased approach the molecular signature leading to myogenic cell defects in DM1. Single cell RNAseq data revealed the presence of a specific subset of DM1 myogenic cells expressing a senescence signature, characterized by the high expression of genes related to senescence-associated secretory phenotype (SASP). This profile was confirmed using different senescence markers in vitro and in situ. The excessive accumulation of intranuclear RNA foci in DM1 senescent cells compared to non-senescent cells suggests that RNA-mediated toxicity contribute to senescence induction. High expression of IL-6, a prominent SASP cytokine, in the serum of DM1 patients was identified as a biomarker correlating with muscle weakness and functional capacity limitations. Drug screening revealed that the BCL-XL inhibitor (A1155463), a senolytic drug, can specifically target senescent DM1 myoblasts to induce their apoptosis and reduce their SASP. Removal of senescent cells re-established the myogenic function of the non-senescent DM1 myoblasts, which displayed improved proliferation and differentiation capacity in vitro; and enhanced engraftment following transplantation in vivo. Altogether this study presents a well-defined senescent molecular signature in DM1 untangling part of the pathological mechanisms observed in the disease; additionally, we demonstrate the therapeutic potential of targeting these defective cells with senolytics to restore myogenesis.

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Section: Methodsmentioning

confidence: 99%

Clearance of defective muscle stem cells by senolytics reduces the expression of senescence-associated secretory phenotype and restores myogenesis in myotonic dystrophy type 1

Conte

Bishop

Orfi

et al. 2022

Preprint

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“…The ICF component with the highest registered needs was environmental factors , with 880 registrations in total. Environmental factors are considered as barriers or facilitators in relation to activity and participation 11,26 . In the present study, assisted aids and personal assistance was the second most common environmental factor, with 250 registrations in total.…”

Section: Discussionmentioning

confidence: 60%

“…In addition to assisted aids and personal assistance , needs regarding residence and life event transitions were also significant environmental factors in the present study. This is underlined by a study by Raymond et al who found that use of community services for adapted transportation and perception of obstacles in the physical environment and accessibility are predictors for reduced participation 11 …”

Section: Discussionmentioning

confidence: 99%

“…Patients with DM1 have known challenges in several domains of participation, such as nutrition, fitness, personal care, mobility, community life and recreation 10 . Common predictors of participation restrictions can be associated with both personal and environmental factors, like lower grip strength, higher body mass index, perceived impact of myotonia in daily living, longer time to stand and walk, perception of obstacles in the physical environment, and accessibility and use of community services of adapted transportation 11 . Due to the complexity of the disease, care recommendations for DM1 have been developed, which set standards for the delivery of health care and rehabilitation, recommending frequent healthcare follow‐ups with various specialists 8,12 …”

Section: Introductionmentioning

confidence: 99%

“…10 Common predictors of participation restrictions can be associated with both personal and environmental factors, like lower grip strength, higher body mass index, perceived impact of myotonia in daily living, longer time to stand and walk, perception of obstacles in the physical environment, and accessibility and use of community services of adapted transportation. 11 Due to the complexity of the disease, care recommendations for DM1 have been developed, which set standards for the delivery of health care and rehabilitation, recommending frequent healthcare follow-ups with various specialists. 8,12 Rehabilitation is defined as 'a set of measures that assist individuals who experience, or are likely to experience, disability to achieve and maintain optimal functioning in interaction with their environments'.…”

Section: Introductionmentioning

confidence: 99%

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A retrospective study of needs and interventions among patients with myotonic dystrophy type 1 in Denmark referred to rehabilitation in the period 2000–2019

Allergodt

Handberg

Frost

et al. 2022

Evaluation Clinical Practice

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Rationale, Aims and Objectives Myotonic dystrophy type 1 (DM1) is a progressive multisystem disorder that requires a special focus on the delivery of health and rehabilitation. The aim of the study was to identify the needs and interventions in patients with DM1 referred to a national rehabilitation hospital and to illustrate the needs and interventions in relation to predefined subgroups of disease classification. Method Electronic medical records from the period 2000−2019 of a randomized sample of patients with DM1 (N = 193) were reviewed to identify rehabilitation needs and interventions. The sample was classified into four subgroups of disease classifications. The number of identified needs and interventions were presented as medians and range, and differences between subgroups were illustrated by Kruskal−Wallis one‐way analysis of variance. The needs were categorized using the International Classification of Functioning, Disability and Health (ICF). Results A total of 2099 needs and 2103 interventions were registered. The most frequent needs were coordination of healthcare services (480) and employment and income (363), while the most frequent interventions were counselling (835) and follow‐up (386). Patients with congenital DM1 had the most needs and interventions per person. In relation to the ICF, the most registered needs were environmental factors (880) and activity and participation (848). Conclusion All subgroups of patients with DM1 had a substantial number of needs and interventions related to coordinating and navigating within the healthcare system. The subgroup of patients with congenital DM1 had the most needs and interventions compared to the other subgroups.

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Comprehensive four-year disease progression assessment of myotonic dystrophy type 1

la Fontaine,

Bruijnes,

Smulders

et al. 2024

Neuromuscular Disorders

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Predictors of participation restriction over a 9-year period in adults with myotonic dystrophy type 1

Abstract: les innovations en sant e (CR-CSIS), Centre int egr e universitaire de sant e et de services sociaux du Saguenay

Cited by 7 publications

References 79 publications

Clearance of defective muscle stem cells by senolytics reduces the expression of senescence-associated secretory phenotype and restores myogenesis in myotonic dystrophy type 1

Clearance of defective muscle stem cells by senolytics reduces the expression of senescence-associated secretory phenotype and restores myogenesis in myotonic dystrophy type 1

A retrospective study of needs and interventions among patients with myotonic dystrophy type 1 in Denmark referred to rehabilitation in the period 2000–2019

Comprehensive four-year disease progression assessment of myotonic dystrophy type 1

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