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What is B7-33 Peptide?
B7-33 is a soluble research peptide taken from the larger, naturally occurring protein H2-relaxin. It is impacting the musculoskeletal system, cardiovascular system, and reproduction. B7-33 retains the anti-fibrotic properties of relaxin without enhancing cAMP production.
B7-33 is more stable and therefore is preferred. It is being investigated as an anti-fibrotic agent in preclinical animal models of liver disease, systemic sclerosis, idiopathic pulmonary fibrosis, and other fibrotic conditions. There are currently five trials of B7-33 in clinical trials for different liver conditions. B7-33 has shown promise in preclinical models of liver disease and the next challenge is to establish how it will perform in human trials.
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How Does B7-33 Work?
B7-33 will have to show efficacy in treating liver fibrosis. It has not been formally tested in this context and it is likely that the disease is being challenged in ways it is not challenged in other liver diseases. The majority of liver disease is due to alcohol and other drugs rather than viral hepatitis and therefore the liver biology is completely different. The fibrotic process in chronic alcoholics appears to differ from that seen in viral hepatitis.
B7-33 Mechanism of action
The mechanisms by which B7-33 reduces fibrosis in models of chronic alcoholism, which are not associated with viral hepatitis, are unknown but may be related to the anti-inflammatory action of B7-33 and reduction of the TGF-β signaling pathway. Furthermore, in alcoholic models of liver disease, B7-33 seems to attenuate liver regeneration ([@B34]), which may be important in preventing a second hepatectomy. Thus, B7-33 is likely to be efficacious in alcoholic liver disease and probably in idiopathic liver fibrosis but will be tested in other disease states.
B7-33 Benefits
B7-33 also attenuates inflammation and oxidative stress. It does not appear to promote hepatic insulin resistance and it is safe in humans. These latter properties make it a potentially attractive alternative to anti-inflammatory drugs such as corticosteroids. It is important to note that the preclinical safety profile of B7-33, which is well established, is likely to be reproduced in humans.
B7-33 Trials
Other therapies in preclinical development for liver fibrosis include galectin-3 which mediates fibrosis and is an interesting therapeutic target since it acts as a ligand for E-cadherin on liver cells. There is one clinical trial in clinical trial in liver fibrosis with a galectin-3 antagonist, RG7213 but it is not known if the compound will reach clinical efficacy. Other therapies targeting inflammation include methotrexate, tetracycline derivatives, and the non-nucleoside antibiotic, doxycycline.
There are no clinical trials with either of these compounds for the treatment of liver fibrosis but the tetracycline derivatives are being evaluated for non-alcoholic steatohepatitis (NASH) in a clinical trial. Another potentially interesting therapy is metformin which decreases the liver injury and fibrosis induced by bile duct ligation and CCl~4~ in mice. It is hoped that further development of this drug will yield a better tolerated and effective therapy.
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B7-33 Peptide for Research Conclusion
A substantial body of preclinical evidence demonstrates that liver fibrosis can be reversed and that the fibrosis is associated with a profibrogenic T-cell population. There are several drugs in development, targeting the fibrogenic T-cell and/or profibrogenic cytokine pathways, for this indication. None are yet in clinical use but some may be in the future. We await the outcome of the first clinical trial in NASH in a couple of years. If the drug has efficacy and safety profile in this condition then it may transform the management of NASH and liver fibrosis. In time, these findings may apply to other liver diseases. A recent report demonstrated that a small molecule that targets the T-cell receptor on T-cell subpopulations prevented fibrosis in several mouse models of fibrosis and the authors called for the development of new molecules that target similar cellular pathways.
