Duchenne muscular dystrophy (DMD), an X-linked dystrophinopathy, is caused by an absence of the muscle cytoskeletal protein dystrophin. Being an inherited neuromuscular disease, it usually affects the pediatric population and leads to muscle degeneration throughout life, due to compromised cell membrane integrity and subsequent cell death. This goes along with chronic inflammation and fibrotic tissue production by fibroblasts surrounding myocytes. Over time, there is a replacement of muscle tissue with fibrotic tissues serving as scar tissue ultimately impacting the individual’s mobility. Interestingly, experimental evidence in both human and rodent models has highlighted a concomitant presence of cognitive, neurological, and autonomic disorders in DMD cases.
The current therapeutic approaches either aim to restore dystrophin expression or to compensate for the lack of dystrophin. Gene therapy for muscular dystrophy, through dystrophin expression restoring, is on its way to approval and CRISPR/Cas9 editing approaches and stem-cell-based cell therapies are also being investigated. However, challenges remain in the effective delivery of therapies, sustained expression, and understanding of the neural implications as the impact on the nervous system and neural degeneration is less explored.
To better understand the pathophysiology, much research has focused on the skeletal muscle cells (myocyte), while Duchenne-associated fibroblasts (DAFs) have received minor research attention. DAFs express altered physiology with a clear impact on their cellular behavior and most importantly, they have been shown to be affected even earlier than myocytes and have a profibrotic phenotype, thereby forming the debilitating scar tissue seen in DMD.
The urge to further explore cellular crosstalk between myocytes/myoblasts and DAFs should emerge in the DMD research community, bridging knowledge gaps that could uncover relevant aspects of the disease helping to tackle fibrosis from an early onset, probably even before skeletal muscle is affected and neural degeneration. The search for therapeutic molecules should focus on the synergy between anti-fibrotic molecules in conjunction with genetic therapy and anti-inflammatory drugs.
This Research Topic aims to examine and investigate different focus points to tackle this challenging neuromuscular disease, with a focus on DAFs, playing a major role in the disease pathophysiology and should be considered equally important as the activated inflammatory cells and the affected myocytes that characterize DMD. Extending the research field of DMD that mainly focuses on myocytes and myotubes to DAFs and the crosstalk between these different cell types, should give important insights into the disease and broaden the therapeutic approaches. Fibroblasts may play a pivotal role in DMD as they can differentiate into neuron-like tissue, fat tissue, myofibroblasts. They may form an important research field in DMD, especially by striving to combine with the ongoing research in DMD myotubes and myocytes. Research in DMD should encompass both the muscular, neural and connective tissues. The intertwining of these cells in DMD should receive much attention in research. Particularly, we aim to deepen our understanding of the impact of the disease on the neural system underlying motor control.
To this aim, we welcome articles addressing the following, but not limited to:
· Role of DAFs as potential markers in DMD early diagnosis.
· Mechanisms underlying DAFs altered physiology leading to early onset profibrotic phenotype.
· Identification of therapeutic molecules with an anti-fibrotic action.
· Intersection of gene therapy and anti-inflammatory therapy: current pros and cons and impact on the nervous system.
· Morpho-functional features underlying neurological disorders associated with DMD.
· DAFs’ proteome in DMD versus healthy skeletal myocytes/myoblasts.
· DAFs’ secretome in DMD versus healthy skeletal myocytes/myoblasts.
· Molecular crosstalk between DAFs and myocytes/myoblasts.
· Molecular crosstalk between DAFs and neurons.
· DAFs’ involvement in the DMD brain.
· DAFs’ impact on the DMD nervous system.
· Synergy of gene therapy and anti-fibrotic therapy in DMD animal models.
Keywords:
Duchenne muscular dystrophy, Duchenne-Associated Fibroblasts, motor control, neuromuscular disease, inflammation, therapeutic molecules
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
Duchenne muscular dystrophy (DMD), an X-linked dystrophinopathy, is caused by an absence of the muscle cytoskeletal protein dystrophin. Being an inherited neuromuscular disease, it usually affects the pediatric population and leads to muscle degeneration throughout life, due to compromised cell membrane integrity and subsequent cell death. This goes along with chronic inflammation and fibrotic tissue production by fibroblasts surrounding myocytes. Over time, there is a replacement of muscle tissue with fibrotic tissues serving as scar tissue ultimately impacting the individual’s mobility. Interestingly, experimental evidence in both human and rodent models has highlighted a concomitant presence of cognitive, neurological, and autonomic disorders in DMD cases.
The current therapeutic approaches either aim to restore dystrophin expression or to compensate for the lack of dystrophin. Gene therapy for muscular dystrophy, through dystrophin expression restoring, is on its way to approval and CRISPR/Cas9 editing approaches and stem-cell-based cell therapies are also being investigated. However, challenges remain in the effective delivery of therapies, sustained expression, and understanding of the neural implications as the impact on the nervous system and neural degeneration is less explored.
To better understand the pathophysiology, much research has focused on the skeletal muscle cells (myocyte), while Duchenne-associated fibroblasts (DAFs) have received minor research attention. DAFs express altered physiology with a clear impact on their cellular behavior and most importantly, they have been shown to be affected even earlier than myocytes and have a profibrotic phenotype, thereby forming the debilitating scar tissue seen in DMD.
The urge to further explore cellular crosstalk between myocytes/myoblasts and DAFs should emerge in the DMD research community, bridging knowledge gaps that could uncover relevant aspects of the disease helping to tackle fibrosis from an early onset, probably even before skeletal muscle is affected and neural degeneration. The search for therapeutic molecules should focus on the synergy between anti-fibrotic molecules in conjunction with genetic therapy and anti-inflammatory drugs.
This Research Topic aims to examine and investigate different focus points to tackle this challenging neuromuscular disease, with a focus on DAFs, playing a major role in the disease pathophysiology and should be considered equally important as the activated inflammatory cells and the affected myocytes that characterize DMD. Extending the research field of DMD that mainly focuses on myocytes and myotubes to DAFs and the crosstalk between these different cell types, should give important insights into the disease and broaden the therapeutic approaches. Fibroblasts may play a pivotal role in DMD as they can differentiate into neuron-like tissue, fat tissue, myofibroblasts. They may form an important research field in DMD, especially by striving to combine with the ongoing research in DMD myotubes and myocytes. Research in DMD should encompass both the muscular, neural and connective tissues. The intertwining of these cells in DMD should receive much attention in research. Particularly, we aim to deepen our understanding of the impact of the disease on the neural system underlying motor control.
To this aim, we welcome articles addressing the following, but not limited to:
· Role of DAFs as potential markers in DMD early diagnosis.
· Mechanisms underlying DAFs altered physiology leading to early onset profibrotic phenotype.
· Identification of therapeutic molecules with an anti-fibrotic action.
· Intersection of gene therapy and anti-inflammatory therapy: current pros and cons and impact on the nervous system.
· Morpho-functional features underlying neurological disorders associated with DMD.
· DAFs’ proteome in DMD versus healthy skeletal myocytes/myoblasts.
· DAFs’ secretome in DMD versus healthy skeletal myocytes/myoblasts.
· Molecular crosstalk between DAFs and myocytes/myoblasts.
· Molecular crosstalk between DAFs and neurons.
· DAFs’ involvement in the DMD brain.
· DAFs’ impact on the DMD nervous system.
· Synergy of gene therapy and anti-fibrotic therapy in DMD animal models.
Keywords:
Duchenne muscular dystrophy, Duchenne-Associated Fibroblasts, motor control, neuromuscular disease, inflammation, therapeutic molecules
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.