Scientists at the University of Sunderland, led by Dr. Maria Teresa Borrello, have developed two experimental drugs—DR-3 and FDR2—that target the enzyme HDAC6.
These drugs have shown promise in halting or reversing liver fibrosis, a condition characterized by the accumulation of scar tissue in the liver.
Research Overview
The research, published in The FEBS Journal, focuses on the role of HDAC6 in liver fibrosis.
HDAC6 is involved in regulating inflammation and the activation of hepatic stellate cells, which are responsible for producing collagen and contributing to scar tissue formation.
By inhibiting HDAC6, the experimental drugs aim to reduce inflammation and prevent the activation of these stellate cells, thereby mitigating fibrosis progression.
Laboratory Findings
In laboratory settings, the HDAC6 inhibitors DR-3 and FDR2 demonstrated high selectivity for HDAC6 over other histone deacetylases.
They effectively reduced markers of hepatic stellate cell activation and fibrogenic gene expression.
Additionally, these compounds increased acetylation of α-tubulin and suppressed TGF-β1-induced SMAD signaling, which are key pathways in fibrosis development.
Ex Vivo Human Liver Models
The efficacy of DR-3 and FDR2 was further validated using human precision-cut liver slices (hPCLS), an ex vivo model that closely mimics human liver tissue.
Treatment with these inhibitors resulted in reduced fibrogenic protein levels and collagen deposition, indicating their potential to reverse existing fibrosis.
Importantly, these effects were achieved without significant toxicity to the liver tissue.
Clinical Implications
The British Liver Trust has welcomed these findings, highlighting their potential to transform care for the UK's estimated two million liver fibrosis patients, many of whom are diagnosed at advanced stages of the disease.
While these results are promising, the drugs are still in the experimental phase and have not yet undergone human clinical trials. Nevertheless, they offer a targeted therapeutic approach that could eventually become a lifesaving treatment worldwide.
Scientists at the University of Sunderland, led by Dr. Maria Teresa Borrello, have developed two experimental drugs—DR-3 and FDR2—that target the enzyme HDAC6.
These drugs have shown promise in halting or reversing liver fibrosis, a condition characterized by the accumulation of scar tissue in the liver.
Research Overview
The research, published in The FEBS Journal, focuses on the role of HDAC6 in liver fibrosis.
HDAC6 is involved in regulating inflammation and the activation of hepatic stellate cells, which are responsible for producing collagen and contributing to scar tissue formation.
By inhibiting HDAC6, the experimental drugs aim to reduce inflammation and prevent the activation of these stellate cells, thereby mitigating fibrosis progression.
Laboratory Findings
In laboratory settings, the HDAC6 inhibitors DR-3 and FDR2 demonstrated high selectivity for HDAC6 over other histone deacetylases.
They effectively reduced markers of hepatic stellate cell activation and fibrogenic gene expression.
Additionally, these compounds increased acetylation of α-tubulin and suppressed TGF-β1-induced SMAD signaling, which are key pathways in fibrosis development.
Ex Vivo Human Liver Models
The efficacy of DR-3 and FDR2 was further validated using human precision-cut liver slices (hPCLS), an ex vivo model that closely mimics human liver tissue.
Treatment with these inhibitors resulted in reduced fibrogenic protein levels and collagen deposition, indicating their potential to reverse existing fibrosis.
Importantly, these effects were achieved without significant toxicity to the liver tissue.
Clinical Implications
The British Liver Trust has welcomed these findings, highlighting their potential to transform care for the UK's estimated two million liver fibrosis patients, many of whom are diagnosed at advanced stages of the disease.
While these results are promising, the drugs are still in the experimental phase and have not yet undergone human clinical trials. Nevertheless, they offer a targeted therapeutic approach that could eventually become a lifesaving treatment worldwide.
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