Comparison of Serum Pharmacodynamic Biomarkers in Prednisone-Versus Deflazacort-Treated Duchenne Muscular Dystrophy Boys

Prednisone (Pred) and Deflazacort (Dfz) are commonly used glucocorticoids (GCs) for Duchenne muscular dystrophy (DMD) treatment and management. While GCs are known to delay the loss of ambulation and motor abilities, chronic use can result in onerous side effects, e.g., weight gain, growth stunting, loss of bone density, etc. Here, we use the CINRG Duchenne natural history study to gain insight into comparative safety of Pred versus Dfz treatment through GC-responsive pharmacodynamic (PD) biomarkers. Longitudinal trajectories of SOMAscan® protein data obtained on serum of DMD boys aged 4 to 10 (Pred: n = 7; Dfz: n = 8) were analyzed after accounting for age and time on treatment. Out of the pre-specified biomarkers, seventeen candidate proteins were differentially altered between the two drugs (p < 0.05). These include IGFBP-2 and AGER associated with diabetes complications, and MMP-3 associated with extracellular remodeling. As a follow-up, IGFBP-2, MMP-3, and IGF-I were quantified with an ELISA using a larger sample size of DMD biosamples (Dfz: n = 17, Pred: n = 12; up to 76 sera samples) over a longer treatment duration. MMP-3 and IGFBP-2 validated the SOMAscan® signal, however, IGF-I did not. This study identified GC-responsive biomarkers, some associated with safety, that highlight differential PD response between Dfz and Pred.

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Long-term follow-up of dysphagia in adult patients with Duchenne muscular dystrophy

European Journal of Paediatric Neurology ◽

10.1016/j.ejpn.2018.06.004 ◽

2018 ◽

Vol 22 (5) ◽

pp. 786-790 ◽

Cited By ~ 2

Author(s):

Yuka Yamada ◽

Michiyuki Kawakami ◽

Ayako Wada ◽

Shogo Fukui ◽

Koshiro Haruyama ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Adult Patients ◽

Long Term Follow Up

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Longitudinal Motor Functional Outcomes and Magnetic Resonance Imaging Patterns of Muscle Involvement in Upper Limbs in Duchenne Muscular Dystrophy

Medicina ◽

10.3390/medicina57111267 ◽

2021 ◽

Vol 57 (11) ◽

pp. 1267

Author(s):

Claudia Brogna ◽

Lara Cristiano ◽

Tommaso Verdolotti ◽

Giulia Norcia ◽

Luana Ficociello ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Duchenne Muscular Dystrophy ◽

Magnetic Resonance ◽

Muscular Dystrophy ◽

Resonance Imaging ◽

Muscle Mri ◽

Functional Changes ◽

One Year ◽

Age Range

Background and Objectives: The aim of this study was to evaluate longitudinal changes using both upper limb muscle Magnetic Resonance Imaging (MRI) at shoulder, arm and forearm levels and Performance of upper limb (PUL) in ambulant and non-ambulant Duchenne Muscular Dystrophy (DMD) patients. We also wished to define whether baseline muscle MRI could help to predict functional changes after one year. Materials and Methods: Twenty-seven patients had both baseline and 12month muscle MRI and PUL assessments one year later. Results: Ten were ambulant (age range 5–16 years), and 17 non ambulant (age range 10–30 years). Increased abnormalities equal or more than 1.5 point on muscle MRI at follow up were found on all domains: at shoulder level 12/27 patients (44%), at arm level 4/27 (15%) and at forearm level 6/27 (22%). Lower follow up PUL score were found in 8/27 patients (30%) at shoulder level, in 9/27 patients (33%) at mid-level whereas no functional changes were found at distal level. There was no constant association between baseline MRI scores and follow up PUL scores at arm and forearm levels but at shoulder level patients with moderate impairment on the baseline MRI scores between 16 and 34 had the highest risk of decreased function on PUL over a year. Conclusions: Our results confirmed that the integrated use of functional scales and imaging can help to monitor functional and MRI changes over time.

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Progression of muscular co-activation and gait variability in children with Duchenne muscular dystrophy: A 2-year follow-up study

Clinical Biomechanics ◽

10.1016/j.clinbiomech.2020.105101 ◽

2020 ◽

Vol 78 ◽

pp. 105101

Author(s):

Martina Rinaldi ◽

Maurizio Petrarca ◽

Alberto Romano ◽

Gessica Vasco ◽

Carmen D'Anna ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Gait Variability ◽

Follow Up Study ◽

Co Activation

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SAT0674 The use of quantitative muscle ultrasound as a follow-up tool in inflammatory myositis and duchenne muscular dystrophy in children

10.1136/annrheumdis-2018-eular.4631 ◽

2018 ◽

Author(s):

W.A. Hassan ◽

A.E.S. Elbrashy ◽

S.S. Ganeb ◽

D.R. Lasheen ◽

E.A. Mohammady

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Inflammatory Myositis ◽

Muscle Ultrasound

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Long-term follow-up of patients with Duchenne muscular dystrophy receiving ventilatory support

Muscle & Nerve ◽

10.1002/mus.880160519 ◽

1993 ◽

Vol 16 (5) ◽

pp. 554-558 ◽

Cited By ~ 13

Author(s):

Hidetoshi Fukunaga ◽

Ryuichi Okubo ◽

Takashi Moritoyo ◽

Nozomu Kawashima ◽

Mitsuhiro Osame

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Ventilatory Support ◽

Long Term Follow Up

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Lung function in ataluren-treated, non-ambulatory patients with nonsense mutation Duchenne muscular dystrophy from a long-term extension trial versus untreated patients from a natural history study

Neuromuscular Disorders ◽

10.1016/s0960-8966(17)30233-x ◽

2017 ◽

Vol 27 ◽

pp. S6

Author(s):

X. Luo ◽

J. McIntosh ◽

P. Trifillis ◽

A. Gill ◽

T. Ong ◽

...

Keyword(s):

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Lung Function ◽

Natural History ◽

Nonsense Mutation ◽

Natural History Study ◽

Ambulatory Patients ◽

Extension Trial

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P294 – 1740 A prospective natural history study of the progression of physical impairment, activity limitation and quality of life in Duchenne muscular dystrophy

European Journal of Paediatric Neurology ◽

10.1016/s1090-3798(13)70473-2 ◽

2013 ◽

Vol 17 ◽

pp. S134

Author(s):

N Goemans ◽

E Mercuri ◽

A Morgan ◽

M Eagle ◽

F Lawrence ◽

...

Keyword(s):

Quality Of Life ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Natural History ◽

Activity Limitation ◽

Physical Impairment ◽

Natural History Study

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Electron microscopy of changes in lower extremity muscles in Duchenne muscular dystrophy

Journal of the American Podiatric Medical Association ◽

10.7547/87507315-81-6-294 ◽

1991 ◽

Vol 81 (6) ◽

pp. 294-299

Author(s):

J Atkin ◽

VW Thompson ◽

RB Boyd

Keyword(s):

Electron Microscopy ◽

Duchenne Muscular Dystrophy ◽

Muscular Dystrophy ◽

Genetic Disease ◽

Extensor Digitorum Longus ◽

Microscopic Level ◽

Electron Microscopic Level ◽

Electron Microscopic ◽

Dystrophic Mice ◽

Insight Into

Duchenne muscular dystrophy is a genetic disease with a sex-linked pattern of inheritance. This disease is present at birth, becomes symptomatic during early childhood, leads to inability to walk near the end of the first decade, and usually results in death by the end of the second decade. In this study, the extensor digitorum longus and soleus muscles from genetically dystrophic mice were examined at the electron microscopic level. The authors describe their results and discuss how these findings might provide some insight into one of the mechanisms of fiber necrosis in Duchenne muscular dystrophy.

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