scholarly journals Therapeutic Strategies Targeting DUX4 in FSHD

2020 ◽  
Vol 9 (9) ◽  
pp. 2886
Author(s):  
Laura Le Gall ◽  
Eva Sidlauskaite ◽  
Virginie Mariot ◽  
Julie Dumonceaux
Keyword(s):  
Skeletal Muscle ◽  
Animal Models ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Therapeutic Strategies ◽  
Lower Body ◽  
Chromosome 4 ◽  
Therapeutic Approaches ◽  
Muscle Dystrophy ◽  
Muscle Involvement ◽  
Research Areas

Facioscapulohumeral muscular dystrophy (FSHD) is a common muscle dystrophy typically affecting patients within their second decade. Patients initially exhibit asymmetric facial and humeral muscle damage, followed by lower body muscle involvement. FSHD is associated with a derepression of DUX4 gene encoded by the D4Z4 macrosatellite located on the subtelomeric part of chromosome 4. DUX4 is a highly regulated transcription factor and its expression in skeletal muscle contributes to multiple cellular toxicities and pathologies ultimately leading to muscle weakness and atrophy. Since the discovery of the FSHD candidate gene DUX4, many cell and animal models have been designed for therapeutic approaches and clinical trials. Today there is no treatment available for FSHD patients and therapeutic strategies targeting DUX4 toxicity in skeletal muscle are being actively investigated. In this review, we will discuss different research areas that are currently being considered to alter DUX4 expression and toxicity in muscle tissue and the cell and animal models designed to date.

scholarly journals Functional Test Scales for Evaluating Cell-Based Therapies in Animal Models of Spinal Cord Injury

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Woon Ryoung Kim ◽  
Minjin Kang ◽  
Heejoo Park ◽  
Hyun-Joo Ham ◽  
Hyunji Lee ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Animal Models ◽  
Functional Assessment ◽  
Therapeutic Strategies ◽  
Assessment Tools ◽  
Therapeutic Approaches ◽  
Behavioral Test ◽  
Cord Injury ◽  
Suitable Animal Model

Recently, spinal cord researchers have focused on multifaceted approaches for the treatment of spinal cord injury (SCI). However, as there is no cure for the deficits produced by SCI, various therapeutic strategies have been examined using animal models. Due to the lack of standardized functional assessment tools for use in such models, it is important to choose a suitable animal model and precise behavioral test when evaluating the efficacy of potential SCI treatments. In the present review, we discuss recent evidence regarding functional recovery in various animal models of SCI, summarize the representative models currently used, evaluate recent cell-based therapeutic approaches, and aim to identify the most precise and appropriate scales for functional assessment in such research.

scholarly journals Current Therapeutic Approaches in FSHD

2020 ◽  
pp. 1-11
Author(s):  
Leo H. Wang ◽  
Rabi Tawil
Keyword(s):  
Skeletal Muscle ◽  
Clinical Trials ◽  
Neuromuscular Diseases ◽  
Underlying Disease ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Muscular Dystrophies ◽  
Therapeutic Approaches ◽  
Disease Mechanism ◽  
First Time ◽  
Targeted Approach

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common muscular dystrophies. Over the last decade, a consensus was reached regarding the underlying cause of FSHD allowing—for the first time—a targeted approach to treatment. FSHD is the result of a toxic gain-of-function from de-repression of the DUX4 gene, a gene not normally expressed in skeletal muscle. With a clear therapeutic target, there is increasing interest in drug development for FSHD, an interest buoyed by the recent therapeutic successes in other neuromuscular diseases. Herein, we review the underlying disease mechanism, potential therapeutic approaches as well as the state of trial readiness in the planning and execution of future clinical trials in FSHD.

scholarly journals Skeletal muscle imaging in facioscapulohumeral muscular dystrophy, pattern and asymmetry of individual muscle involvement

2014 ◽  
Vol 24 (12) ◽  
pp. 1087-1096 ◽  
Author(s):  
N.H.M. Rijken ◽  
E.L. van der Kooi ◽  
J.C.M. Hendriks ◽  
R.J.G.P. van Asseldonk ◽  
G.W. Padberg ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Facioscapulohumeral Muscular Dystrophy ◽  
Muscle Involvement ◽  
Individual Muscle

Skeletal muscle involvement in tropical spastic paraparesis/HTLV-1-associated myelopathy

1994 ◽  
Vol 17 (8) ◽  
pp. 923-930 ◽  
Author(s):  
Alberto Alain Gabbai ◽  
Clayton A. Wiley ◽  
Acary S. B. Oliveira ◽  
Ricardo Smith ◽  
Beny Schmidt ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Spastic Paraparesis ◽  
Tropical Spastic Paraparesis ◽  
Muscle Involvement ◽  
Skeletal Muscle Involvement

Relationship between Thyroid Function and Skeletal Muscle Involvement in Subclinical and Overt Hypothyroidism

2001 ◽  
Vol 11 (3) ◽  
pp. 217-221 ◽  
Author(s):  
Elisabeth Hartl ◽  
Josef Finsterer ◽  
Carmen Grossegger ◽  
Alois Kroiss ◽  
Claudia Stöllberger
Keyword(s):  
Skeletal Muscle ◽  
Thyroid Function ◽  
Overt Hypothyroidism ◽  
Muscle Involvement ◽  
Skeletal Muscle Involvement

scholarly journals THU0358 NEGATIVE CHANGES OF BODY COMPOSITION IN MYOSITIS PATIENTS AND THEIR ASSOCIATION WITH DISEASE SPECIFIC CHARACTERISTICS, PHYSICAL ACTIVITY AND NUTRITIONAL STATUS.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 410.3-410
Author(s):  
S. Oreska ◽  
M. Špiritović ◽  
P. Česák ◽  
O. Marecek ◽  
H. Štorkánová ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Body Composition ◽  
Lipid Metabolism ◽  
Nutritional Status ◽  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Disease Duration ◽  
Serum Levels ◽  
Muscle Involvement

Background:Skeletal muscle, pulmonary and articular involvement in idiopathic inflammatory myopathies (IIM) limit the mobility/self-sufficiency of patients, and can have a negative impact on body composition.Objectives:The aim was to assess body composition and physical activity of IIM patients and healthy controls (HC) and the association with selected inflammatory cytokines/chemokines and laboratory markers of nutrition and lipid metabolism.Methods:54 patients with IIM (45 females; mean age 57.7; disease duration 5.8 years; polymyositis (PM, 22) / dermatomyositis (DM, 25) / necrotizing myopathy (IMNM, 7)) and 54 age-/sex-matched HC (45 females, mean age 57.7) without rheumatic/tumor diseases were included. PM/DM patients fulfilled Bohan/Peter criteria for PM/DM. We assessed body composition (densitometry: iDXA Lunar, bioelectric impedance: BIA2000-M), physical activity (Human Activity Profile, HAP questionnaire), serum levels of 27 cytokines/chemokines (commercial multiplex ELISA kit, Bio-Rad Laboratories) and serum levels of selected parameters of nutrition and lipidogram. Disease activity (MITAX and MYOACT activity score) and muscle involvement (manual muscle testing, MMT-8, and functional index 2, FI2) were evaluated. Data are presented as mean±SD.Results:Compared to HC, patients with IIM had a trend towards significantly increased body fat % (BF%; iDXA: 39.9±7.1 vs. 42.4±7.1 %, p=0.077), but significantly decreased lean body mass (LBM; iDXA: 45.6±8.1 vs. 40.6±7.2 kg, p=0.001; BIA: 52.6±8.8 vs. 48.7±9.0 kg, p=0.023), increased extracellular mass/body cell mass (ECM/BCM) ratio (1.06±0.15 vs. 1.44±0.42, p<0.001), reflecting deteriorated nutritional status and predisposition for physical activity, and significantly lower bone mineral density (BMD: 1.2±0.1 vs. 1.1±0.1 g/cm2, p<0.001). Disease duration negatively correlated with BMD and LBM-BIA. Disease activity (MITAX, MYOACT) positively correlated with LBM (by BIA and DXA), similarly as with basal metabolic rate (BMR), and fat free mass (FFM). CRP was positively associated with BF% (BIA and DXA). Higher BF%-DEXA was associated with worse physical endurance (FI2) and worse ability to perform physical activity (HAP). MMT-8 score negatively correlated with ECM/BCM ratio. Serum levels of several inflammatory cytokines/chemokines (specifically IL-1ra, MCP, IL-10) and markers of nutrition (specifically albumin, C3-, C4-complement, cholinesterase, amylase, insulin and C-peptide, vitamin-D, orosomucoid), and lipid metabolism (specifically triglycerides, high-density lipoprotein, apolipoprotein A and B, atherogenic index of plasma) were significantly associated with alterations of body composition in IIM patients. (p<0.05 for all correlations)Conclusion:Compared to healthy age-/sex-matched individuals we found significant negative changes in body composition of our IIM patients associated with their disease activity and duration, inflammatory status, skeletal muscle involvement, and physical activity. These data could reflect their impaired nutritional status and predispositions for physical exercise, aerobic fitness and performance.Serum levels of certain inflammatory cytokines/chemokines and markers of nutrition and lipid metabolism were associated with alterations of body composition in IIM patients. This might further support the role of systemic inflammation and nutritional status on the negative changes in body composition of IIM patients.Acknowledgments:Supported by AZV NV18-01-00161A, MHCR 023728, SVV 260373 and GAUK 312218Disclosure of Interests:Sabina Oreska: None declared, Maja Špiritović: None declared, Petr Česák: None declared, Ondrej Marecek: None declared, Hana Štorkánová: None declared, Barbora Heřmánková: None declared, Kateřina Kubinova: None declared, Martin Klein: None declared, Lucia Vernerová: None declared, Olga Růžičková: None declared, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Ladislav Šenolt: None declared, Heřman Mann: None declared, Jiří Vencovský: None declared, Michal Tomčík: None declared

scholarly journals Therapeutic Effects of Hydrogen in Animal Models of Parkinson's Disease

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Kyota Fujita ◽  
Yusaku Nakabeppu ◽  
Mami Noda
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Models ◽  
Animal Studies ◽  
Clinical Symptoms ◽  
Therapeutic Effects ◽  
Therapeutic Approaches ◽  
Cellular Apoptosis ◽  
6 Hydroxydopamine

Since the first description of Parkinson's disease (PD) nearly two centuries ago, a number of studies have revealed the clinical symptoms, pathology, and therapeutic approaches to overcome this intractable neurodegenerative disease. 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA) are neurotoxins which produce Parkinsonian pathology. From the animal studies using these neurotoxins, it has become well established that oxidative stress is a primary cause of, and essential for, cellular apoptosis in dopaminergic neurons. Here, we describe the mechanism whereby oxidative stress evokes irreversible cell death, and propose a novel therapeutic strategy for PD using molecular hydrogen. Hydrogen has an ability to reduce oxidative damage and ameliorate the loss of nigrostriatal dopaminergic neuronal pathway in two experimental animal models. Thus, it is strongly suggested that hydrogen might provide a great advantage to prevent or minimize the onset and progression of PD.

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