Both Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) are neuromuscular diseases. DMD is a severe X-linked disorder characterized by the absence of dystrophin, a crucial muscle cytoskeletal protein. Predominantly affecting the pediatric population, DMD leads to progressive muscle degeneration due to compromised cell membrane integrity and subsequent cell death. This degeneration is accompanied by chronic inflammation and the production of fibrotic tissue by fibroblasts, which replace healthy muscle tissue over time, severely impacting mobility. Recent studies have also identified cognitive, neurological, and autonomic disorders associated with DMD, suggesting a broader systemic impact. Current therapeutic strategies focus on restoring dystrophin expression or compensating for its absence, with gene therapy and CRISPR/Cas9 editing showing promise. However, challenges remain in effective delivery, sustained expression, and understanding the neural implications of DMD. Most forms of SMA are caused by mutations of the survival motor neuron 1 gene (SMN1) on the fifth chromosome, resulting in insufficient expression levels of the SMN protein. SMN is essential to normal motor function because it enables muscles to receive signals from the nerves.

While much research has focused on skeletal muscle cells, Duchenne-associated fibroblasts (DAFs) have been relatively understudied as compared to SMA fibroblasts, despite their early involvement in fibrosis and potential role in disease progression. Addressing the cellular crosstalk between myocytes and DAFs could provide critical insights into DMD pathophysiology and open new therapeutic avenues.

This Research Topic aims to explore the multifaceted role of Duchenne-associated fibroblasts (DAFs) in DMD and further enhance research on SMA fibroblasts, emphasizing their significance alongside myocytes and inflammatory cells. By extending the research focus to include DAFs and their interactions with other cell types, we seek to uncover novel insights into the disease's progression of DMD and broaden therapeutic strategies. The research will delve into the potential of fibroblasts to differentiate into various cell types and their role in forming debilitating scar tissue. Additionally, the study aims to enhance our understanding of DMD's impact on the neural system, particularly concerning motor control, and to identify therapeutic molecules that can synergize with genetic and anti-inflammatory therapies.

To gather further insights into the complex interplay of cellular components in DMD and SMA, we welcome articles addressing, but not limited to, the following themes:

- Role of DAFs as potential markers in DMD early diagnosis.
- Biomarkers that document treatment-induced effects in SMA.
- Role of SMA fibroblasts in disease progression.
- Mechanisms underlying DAFs' altered physiology leading to early-onset profibrotic phenotype.
- ‎ Mechanisms underlying SMA fibroblasts altered mitochondrial function.
- Identification of therapeutic molecules with anti-fibrotic action for DMD or SMA.
- 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 or SMA.
- 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 SMA fibroblasts and myocytes/myoblasts.
- Molecular crosstalk between DAFs and neurons.
- Molecular crosstalk between SMA fibroblasts 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.
- Synergy of gene therapy and anti-fibrotic therapy in SMA animal models.

Are you interested in contributing a manuscript to this Research Topic?

Fibroblast pathobiology in Duchenne and SMA: Cellular crosstalk and targets for therapeutic intervention