Three Novel Immune-deficient Mouse Models of Muscular Dystrophy
This study provides three novel severely immune-deficient mouse muscular dystrophy models that will be useful in the development of successful gene and cell therapies. We also characterize the models to provide valuable baseline phenotypic information about them. Comparing the results between strains may elucidate further the phenotypic differences between these three forms of muscular dystrophy, although we note that since the strains are not fully inbred, differences in modifier genes may be present between them that could affect phenotype.
Materials and Methods
Ethics statement
The Stanford Administrative Panel o...
Source: PLOS Currents Muscular Dystrophy - September 1, 2017 Category: Neurology Authors: cpichav Source Type: research
Three Novel Immune-deficient Mouse Models of Muscular Dystrophy
This study provides three novel severely immune-deficient mouse muscular dystrophy models that will be useful in the development of successful gene and cell therapies. We also characterize the models to provide valuable baseline phenotypic information about them. Comparing the results between strains may elucidate further the phenotypic differences between these three forms of muscular dystrophy, although we note that since the strains are not fully inbred, differences in modifier genes may be present between them that could affect phenotype.
Materials and Methods
Ethics statement
The Stanford Administrative Panel o...
Source: PLOS Currents Muscular Dystrophy - September 1, 2017 Category: Neurology Authors: cpichav Source Type: research
[MD-17-0009] The PJ Nicholoff Steroid Protocol for Duchenne and Becker Muscular Dystrophy and Adrenal Suppression
Conclusion
This protocol, on how to manage patients with corticosteroid dependence, particularly during periods of stress and how to recognize and prevent an acute adrenal crisis, was named in honor of the late Philip James “PJ” Nicholoff, for his contribution to the global Duchenne community. Despite the tragic loss of PJ’s life, the “PJ Nicholoff Steroid Protocol” is a positive result that will impact the lives of people living with Duchenne and using corticosteroids around the world. We thank PJ and his family for encouraging the development of this resource.
A pdf of the PJ Nicholoff Protocol can be dow...
Source: PLOS Currents Muscular Dystrophy - June 27, 2017 Category: Neurology Authors: Kathi Kinnett Source Type: research
The PJ Nicholoff Steroid Protocol for Duchenne and Becker Muscular Dystrophy and Adrenal Suppression
Conclusion
This protocol, on how to manage patients with corticosteroid dependence, particularly during periods of stress and how to recognize and prevent an acute adrenal crisis, was named in honor of the late Philip James “PJ” Nicholoff, for his contribution to the global Duchenne community. Despite the tragic loss of PJ’s life, the “PJ Nicholoff Steroid Protocol” is a positive result that will impact the lives of people living with Duchenne and using corticosteroids around the world. We thank PJ and his family for encouraging the development of this resource.
A pdf of the PJ Nicholoff Protocol can be dow...
Source: PLOS Currents Muscular Dystrophy - June 27, 2017 Category: Neurology Authors: Kathi Kinnett Source Type: research
Duchenne Regulatory Science Consortium Meeting on Disease Progression Modeling for Duchenne Muscular Dystrophy
Conclusions
The group concluded that they were interested in pursuing such a modeling approach based on consideration of muscle fat fraction, timed function tests, muscle strength, as well as optimized scales of function in ambulant and non-ambulant patients, with additional consideration of time to event analyses of specific disease milestones. The variables that are finally included in the model will be dictated by the data – both what data is in the integrated dataset and what early stage analyses of that data tells us about what is most relevant to the final model. The context of use of the model would be to forecast...
Source: PLOS Currents Muscular Dystrophy - January 12, 2017 Category: Neurology Authors: Jane Larkindale Source Type: research
New Recommendation on Biological Materials Could Hamper Muscular Dystrophy Research
Conclusions
If Recommendation 12.1 is applied to children, it would unduly restrict rare disease research by preventing the use of children’s biomaterials in research involving adults, or on anyone without the same condition and thereby constrict children’s right to benefit from the solidaristic actions of others. It would make efforts to improve data and biomaterials sharing for rare diseases more complex, time consuming and less efficient. Platforms such as RD Connect and BBMRI-ERIC which were designed to contribute to the efficacy and excellent of European research by easing access to resources, could be rendered le...
Source: PLOS Currents Muscular Dystrophy - December 21, 2016 Category: Neurology Authors: Pauline McCormack Source Type: research
Can Quantitative Muscle Strength and Functional Motor Ability Differentiate the Influence of Age and Corticosteroids in Ambulatory Boys with Duchenne Muscular Dystrophy?
Conclusion
The baseline data analysis of this natural history study indicates that the outcomes measures utilized in this study were sensitive to the age related differences in strength and motor function that are characteristic of disease progression boys with DMD; however treatment effects were less likely to be identified. These findings reflect the difficulty inherent in obtaining the statistical power needed to substantiate intervention efficacy in the small, heterogeneous samples sizes that are characteristic of DMD clinical studies. Isokinetic dynamometry revealed variability in the muscles affected, which has been ...
Source: PLOS Currents Muscular Dystrophy - July 8, 2016 Category: Neurology Authors: cbuckon Source Type: research
Prednisone and Deflazacort in Duchenne Muscular Dystrophy: Do They Play a Different Role in Child Behavior and Perceived Quality of Life?
In this study, we only used the syndrome scales of the CBCL. Syndromes are sets of concurrent problems that tend to co-occur together. Syndrome scales include anxious/depressed, withdrawn/depressed, somatic complaints, social problems, thought problems, attention problems, rule-breaking behavior and aggressive behavior. Syndrome scales are categorized into internalizing and externalizing behaviors. Internalizing behaviors are problems that are primarily within the individual and include anxious/depressed, withdrawn/depressed and somatic complaints, while externalizing behaviors are problems that mainly involve conflict wit...
Source: PLOS Currents Muscular Dystrophy - June 17, 2016 Category: Neurology Authors: Susan Sienko Source Type: research
Investigating Synthetic Oligonucleotide Targeting of Mir31 in Duchenne Muscular Dystrophy
In conclusion, it could reasonably be argued that if higher oligo doses are required for miR31-modulation, such doses might well be better reserved for exon skipping in the first place. While miR31-modulation potentially offers a universally-applicable therapeutic for DMD, the levels of oligo ostensibly required (as shown here) would unfortunately seem to render this approach impractical under current oligonucleotide chemistries. A recent study (published after the work described here) further showed that several microRNAs may jointly contribute to suppression of dystrophin translation in BMD, including miR146b and miR374a...
Source: PLOS Currents Muscular Dystrophy - June 16, 2016 Category: Neurology Authors: John CW Hildyard Source Type: research
A Modified Wire Hanging Apparatus for Small Animal Muscle Function Testing
Discussion
The wire hanging test is based on the natural instinct of a mouse to avoid falling. The time that a mouse can hang for is determined by a number of factors, including the physical properties of the muscles, the number of limbs used and the weight of the mouse, as well as age and sex. Muscle disease such as muscular dystrophy, reduces hang times providing a rationale for using the test to determine the potential benefits of interventions. Mouse age and sex can be controlled in the experimental design, and weight can be accounted for in various ways in calculating the result. However, whether a mouse uses two or f...
Source: PLOS Currents Muscular Dystrophy - May 2, 2016 Category: Neurology Authors: efhoffman Source Type: research
Increased taurine in pre-weaned juvenile mdx mice greatly reduces the acute onset of myofibre necrosis and dystropathology and prevents inflammation
Discussion
Taurine administration to juvenile mdx mice from 14 days of age substantially increased muscle taurine content and greatly mitigated the severity of the acute onset of myofibre necrosis and prevented muscle inflammation at 22 days of age. These data are novel and provide strong support for the growing interest in taurine as a potential low cost clinical intervention to protect the muscles of growing DMD boys.
We have previously reported a taurine deficiency in young 18 day old mdx mice, prior to the acute onset of pathology, and this deficiency coincided with the time of weaning of pups from taurine rich mil...
Source: PLOS Currents Muscular Dystrophy - April 29, 2016 Category: Neurology Authors: jessicaterrill Source Type: research
Investigating Synthetic Oligonucleotide Targeting of Mir31 in Duchenne Muscular Dystrophy
In conclusion, it could reasonably be argued that if higher oligo doses are required for miR31-modulation, such doses might well be better reserved for exon skipping in the first place. While miR31-modulation potentially offers a universally-applicable therapeutic for DMD, the levels of oligo ostensibly required (as shown here) would unfortunately seem to render this approach impractical under current oligonucleotide chemistries. A recent study (published after the work described here) further showed that several microRNAs may jointly contribute to suppression of dystrophin translation in BMD, including miR146b and miR374a...
Source: PLOS Currents Muscular Dystrophy - March 8, 2016 Category: Neurology Authors: John CW Hildyard Source Type: research
Dysferlinopathy Fibroblasts Are Defective in Plasma Membrane Repair
In conclusion, fibroblasts from dysferlinopathy patients and SJL mice showed attenuated membrane repair, and could be a research tool to monitor the effects of drug candidate including proteasome inhibitors on mutant dysferlin.
Competing Interests
The authors have declared that no competing interests exist.
Correspondence
The corresponding author can be contacted at cmatsuda@ncnp.go.jp. (Source: PLOS Currents Muscular Dystrophy)
Source: PLOS Currents Muscular Dystrophy - October 29, 2015 Category: Neurology Authors: Chie Matsuda Source Type: research
Enhanced Reprogramming Efficiency and Kinetics of Induced Pluripotent Stem Cells Derived from Human Duchenne Muscular Dystrophy
This study laid the preliminary findings that can be further extended to combine the ex-vivo gene and autologous cell therapy to exploit the therapeutic way to treat DMD that avoid immune rejection with sufficient engraftment ability 40,4. Also, the immaculate expertise in patient-derived iPSCs can accelerate the possibility of personalized medicine in the clinical arena.
Competing Interests
The authors indicate no potential conflicts of interest.
Author Information
Corresponding Author: Sujata Mohanty, Ph.D.
Complete Mailing Address: Stem Cell Facility, 1st Floor ORBO Complex,
All India Institute of Medical Sc...
Source: PLOS Currents Muscular Dystrophy - September 3, 2015 Category: Neurology Authors: Pooja Teotia Source Type: research
