Patients with Duchenne muscular dystrophy (DMD) may benefit from new research into the genetic and immune patterns driving inflammation and scarring in the disease, according to a study published recently in Biochemical and Biophysical Research Communications.
These results show that a natural compound called hesperidin can reduce some of the harmful molecular activity in muscle cells, suggesting a possible pathway for future therapies.
Researchers began by examining muscle gene activity and found 2,187 genes that differed between patients and controls. Of these, 1,385 were increased and 802 were decreased, signaling major changes in how DMD muscle functions.
Using a tool called weighted gene co-expression network analysis, they grouped genes by similar behavior. Nine clusters emerged, and one stood out: the turquoise module, which showed a strong correlation with DMD status. Genes in this module were also tightly connected to each other and to the disease.
To narrow the list further, the team compared differentially expressed genes, module members and disease-related genes from the GeneCards database. This intersection produced 117 highly relevant genes. After building a protein interaction network and applying several ranking methods, they identified 26 core hub genes. Additional statistical modeling reduced these to five especially important genes: CXCL12, PTPRC, SPP1, CD86 and COL1A1.
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Enrichment analyses showed that these genes drive processes linked to inflammation, cell adhesion, the extracellular matrix and pathways such as PI3K-Akt, which plays a major role in muscle survival and regeneration. Immune cell profiling revealed increases in exhausted T cells, γδ T cells, natural killer cells and CD8 T cells, with decreases in central memory T cells, dendritic cells and regulatory T cells. This pattern reflects heightened immune attack paired with weakened immune control.
Single-cell analysis validated these findings in mouse muscle, identifying 14 clusters representing major cell types, including fibroblasts, proliferating muscle stem cells and immune cells. These cell groups showed concentrated expression of the hub genes, reinforcing their central role in DMD injury and repair.
Hesperidin was tested in muscle cells exposed to inflammatory stress. It improved cell survival and reduced the expression of four of the five hub genes, supporting early evidence that it may help calm damaging inflammation. While not yet a treatment, this work offers a clearer picture of disease behavior and points to new therapeutic possibilities for patients and families living with DMD.
“Hesperidin was shown to alleviate inflammatory injury and downregulate these hub genes in vitro, supporting its potential as a therapeutic candidate,” explained this study’s authors. “These findings provide novel molecular targets and a rationale for modulating the immune–fibrotic microenvironment in DMD.”
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