In this interview, Robert Sarkany, MD, FRCP, explains the biology behind erythropoietic protoporphyria and how PORT-77 targets its underlying cause.
Erythropoietic protoporphyria (EPP) causes lifelong, severe phototoxic pain and, in a subset of patients, progressive liver disease, according to Robert Sarkany, MD, FRCP, a consultant dermatologist and senior photodermatology consultant at St John's Institute of Dermatology, Guy's and St Thomas' Hospital, London, who has researched the condition for more than 3 decades.1
Sarkany touched on
Protoporphyrin carries 2 distinct forms of toxicity, according to Sarkany. In the skin, protoporphyrin circulating in superficial blood vessels generates free radical species upon exposure to blue or violet light, damaging vascular endothelium and triggering severe pain episodes.
In the liver, protoporphyrin excreted into bile accumulates at high concentrations and proves toxic to bile canalicular cells independent of light exposure. Sarkany noted 100% of patients with EPP experience severe, treatment-resistant burning pain lasting 3 - 4 days, while approximately 3% progress to cirrhotic liver disease and eventual liver failure requiring transplantation.
PORT-77 targets ABCG2, a transporter previously known as the breast cancer resistance protein, which Sarkany said was found to actively pump protoporphyrin out of red blood cells and into plasma rather than allowing passive diffusion, as previously assumed.
By inhibiting ABCG2, PORT-77 is designed to prevent this efflux and lower plasma protoporphyrin concentrations. Sarkany explained the therapeutic theory rests on the fact plasma is the compartment in direct contact with both vascular endothelium in the skin and bile canalicular cells and hepatocytes in the liver, meaning reduced plasma levels could protect against toxicity in both organ systems.
Editor's Note: This transcript has been edited for grammar and clarity using artificial intelligence tools.
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