Research Background

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare genetic skin disorder caused by mutations in the COL7A1 gene, leading to the absence or dysfunction of type VII collagen (C7). Type VII collagen is a crucial protein for maintaining skin structural stability, and its deficiency makes patients’ skin extremely fragile, prone to blistering and chronic wounds. Chronic wounds not only severely impair patients’ quality of life but also trigger inflammation, tissue scarring, and an increased risk of skin cancer. Therefore, effectively promoting wound healing in RDEB patients is an urgent issue.

Matrix metalloproteinase-9 (MMP-9) plays a significant role in the inflammation and healing processes of chronic wounds. Studies have shown that MMP-9 expression is significantly elevated in keratinocytes of RDEB patients, which may be a key factor contributing to impaired wound healing. Diacerein, a small-molecule drug approved for the treatment of rheumatoid arthritis, exerts anti-inflammatory effects by inhibiting the interleukin-1β (IL-1β) signaling pathway. Due to its known mechanism of action and favorable safety profile, diacerein is considered a potential treatment for RDEB patients.

Research Source

This paper was co-authored by researchers, including Sonja Dorfer and Michael Ablinger from the Department of Dermatology and Allergology at the University Hospital Salzburg in Austria, and was published in the Journal of Dermatology in 2025. The study was funded by DEBRA Alto Adige and DEBRA Austria.

Research Process and Results

1. Patient Treatment Case

The study involved a 5-year-old RDEB patient with extensive chronic wounds on the back. The patient was treated with 1% diacerein ointment topically for 4 weeks. During treatment, the parents recorded wound healing progress and took photographs.

Results: The patient’s skin condition improved significantly after 2 days of treatment. After 4 weeks, nearly all wounds had healed except for one coin-sized lesion. Additionally, the patient’s quality of life improved markedly, with reduced itching, improved sleep quality, increased daytime energy, and other benefits.

2. In Vitro Experiments with Keratinocytes

Keratinocytes were isolated from skin biopsies of the patient (RDEB-223-KC) and a healthy control (HC-1090-KC) for in vitro culture. MMP-9 mRNA and protein expression levels were measured using real-time quantitative PCR and Western blot.

Results: In RDEB patient keratinocytes, MMP-9 mRNA levels showed no significant difference, but protein levels were significantly higher than in controls, indicating post-transcriptional upregulation of MMP-9 expression.

3. LPS and IL-1β Stimulation Experiments

The study used lipopolysaccharide (LPS) and recombinant IL-1β to stimulate RDEB patient keratinocytes to observe their effects on MMP-9 expression.

Results: Both LPS and IL-1β significantly induced MMP-9 expression, suggesting that inflammatory responses may play a critical role in wound chronicity in RDEB patients.

4. Diacerein’s Regulatory Effect on MMP-9

RDEB patient keratinocytes were cultured with 10 μg/ml diacerein for 24 hours, and MMP-9 expression levels were measured.

Results: Diacerein significantly reduced MMP-9 protein expression, indicating its potential to promote wound healing by inhibiting MMP-9.

5. Matrix Degradation Assay

RDEB patient keratinocytes were seeded in a fibrin matrix to observe their matrix degradation capacity under the influence of diacerein and LPS.

Results: Cells treated with diacerein showed significantly reduced matrix degradation, while LPS-treated cells exhibited enhanced degradation. Co-treatment with diacerein and LPS counteracted the LPS-induced matrix degradation.

6. Skin Tissue Section Analysis

Immunofluorescence staining was performed on chronic wound tissue sections from a 31-year-old RDEB patient to detect MMP-9 and IL-1β expression.

Results: MMP-9 and IL-1β expression was significantly higher at the wound edge compared to non-lesional areas, further supporting the role of MMP-9 in RDEB wound chronicity.

Research Conclusions

This study demonstrates that diacerein significantly improves wound healing in RDEB patients by inhibiting MMP-9 expression. This finding provides a new direction for RDEB treatment, particularly in intervention for chronic wounds.

Research Highlights

1. Clinical Significance: This is the first report on the therapeutic potential of diacerein in RDEB patients, offering a new treatment option for this rare disease.
2. Mechanistic Insights: The study detailed the molecular mechanism by which diacerein promotes wound healing through MMP-9 inhibition.
3. Comprehensive Validation: Combining clinical cases, in vitro experiments, and histological analysis, the study comprehensively validated the therapeutic efficacy and mechanism of diacerein.

Research Value

This study not only offers new hope for RDEB patients but also provides insights for other diseases related to chronic wounds. Additionally, the drug repurposing strategy accelerates the clinical application of diacerein, offering a new approach to drug development for rare diseases.