A common antihistamine, chlorcyclizine, may offer a new treatment avenue for erythropoietic protoporphyria (EPP), a rare genetic disease that can cause severe liver damage. This finding comes from research conducted by Rutgers Health and published in Cellular and Molecular Gastroenterology and Hepatology.
Bishr Omary, senior vice chancellor for academic affairs and research at Rutgers Health, highlighted the need for alternative treatments: “There is an unmet need for these patients.” Currently, liver transplantation is the primary treatment for those with severe liver damage due to EPP. However, this procedure relies on available donor organs.
EPP affects approximately 4,000 individuals in the United States. Only a small fraction of these patients experience liver damage severe enough to necessitate transplantation. Due to its rarity, drug development specifically targeting EPP is unlikely. Therefore, Omary’s team explored existing medications.
The researchers screened over 2,500 compounds using a zebrafish larvae model developed by Omary’s lab. The transparency of zebrafish larvae allows easy visualization of toxic compound buildup and assessment of potential treatments. Ning Kuo, first author of the study, explained: “If I saw glowing porphyrin, the treatment didn’t work.”
In tests on mice with EPP, chlorcyclizine reduced hepatic protoporphyrin accumulation and liver injury in female mice but not in males. This difference is attributed to faster metabolism of the drug in male livers. Omary noted: “Fortunately, we’re not aware of similar chlorcyclizine metabolism differences in humans.”
The study also showed that chlorcyclizine works through multiple mechanisms including reducing inflammation and aiding the liver in clearing toxic porphyrin buildup. The findings suggest that antihistamines could prevent early-stage liver damage in EPP patients.
Researchers aim to initiate clinical trials to test chlorcyclizine’s effectiveness for both liver and skin symptoms in EPP patients. A phase 2 trial is already underway testing cimetidine for skin manifestations of EPP. Kuo expressed optimism about future trials: “Given their well-established safety, we hope to fast-track trials of chlorcyclizine either alone or in combination with cimetidine.”
