Longitudinal data have been published in 2 cohorts of DMD patients in Canada, Montreal and Toronto (8-12, 18). Deflazacort treatment benefitted both cohorts with prolonged ambulation, preserved cardiac and respiratory function, less scoliosis and improved survival. Common side effects reported include increased weight gain,

decreased height and cataract formation. It is unclear how deflazacort affects bone health. Delayed puberty was not commented on. There were no reported problems Inhibitors,research,lifescience,medical with wound healing, increased bacterial or viral selleck chemicals Lenalidomide infections, diabetes or glucosuria. Standards of care across Canada are quite similar. The Canadian experience supports the use of deflazacort in treating boys with DMD.
The mdx mouse has a premature stop codon mutation on exon 23 of the dystrophin gene, leading to a lack of the mature protein. The absence of dystrophin results in an acute onset of skeletal muscle necrosis around 3 weeks of post-natal life, followed by an extensive period of degeneration and regeneration until necrosis gradually decreases and a relatively Inhibitors,research,lifescience,medical low level is reached in adult mice (3-4 months)

with pathology stabilization. The pathology is far more benign than in DMD, and cardiomyopathy and fibrosis appear only in very late stage of the disease. The benign phenotype of the mdx mouse raises the Inhibitors,research,lifescience,medical main concerns about its appropriateness for pre-clinical studies; in fact drug effects can be hardly estimated while no clear consensus exists about the readout parameters that are more predictable for the human disease. In addition, a large variability exists between the experimental approaches used by various research groups and this, together with the high inter- and intra-individual variability of pathology, makes difficult Inhibitors,research,lifescience,medical Inhibitors,research,lifescience,medical to compare results obtained

in different laboratories. A detailed discussion about this topic is out of the scope of the present review. More specific reviews are available describing the effort of focused experts panels to find a consensus on the most reliable approach Brefeldin_A to enhance data predictability in mdx mouse (www.treat-nmd.eu/research/pre-clinical/SOPs [6-8]). Accordingly, standardized protocols for the assessment of various endpoints resulted from specialized working groups of experts and are available on www.treat-nmd.eu/research/pre-clinical/SOPs. Importantly to mention is the consensus raised around the protocol of forced exercise on horizontal treadmill, as the one in use in the laboratory of this review’s author, as a strategy to prolong the degenerative phase and then to enhance patient’s like alterations useful for pre-clinical evaluation of therapeutics (6, 9). This is based on the hypothesis of contractile susceptibility of dystrophic muscle, and is supported by the more severe signs in the mdx diaphragm which undergoes a continuous respiratory activity (6).