AdhMMP8 Vector Administration in Muscle: An Alternate Strategy to Regress Hepatic Fibrosis

Area of Science:

• Biomedical Engineering
• Gene Therapy
• Hepatology

Background:

• Advanced liver fibrosis involves scar tissue replacing liver cells, driven by pro-inflammatory and pro-fibrotic gene expression.
• Matrix metalloproteinase 8 (MMP-8) is an enzyme that degrades collagen type I, a key component of scar tissue.

Purpose of the Study:

• To investigate the therapeutic effects of intramuscularly delivered adenoviral vector containing proMMP-8 gene cDNA (AdhMMP8) on experimental advanced liver fibrosis in rats.

Main Methods:

• Male Wistar rats with thioacetamide-induced liver fibrosis received a single intramuscular dose of AdhMMP8.
• Therapeutic effects were assessed 1, 2, and 3 weeks post-administration by measuring fibrosis, protein concentrations, and gene expression.

Main Results:

• Hepatic fibrosis decreased by up to 48% with AdhMMP8 treatment.
• Expression of pro-inflammatory (TNF-α, IL-1) and pro-fibrotic (Col1A1, TGF-β1, CTGF) genes significantly diminished.
• Expression of anti-fibrotic genes (MMP-9, MMP-1) increased.

Conclusions:

• Intramuscular AdhMMP8 administration is a safe and effective method for liver fibrosis regression.
• This minimally invasive gene therapy approach achieves comparable results to systemic delivery for treating liver fibrosis.