Protoporphyrin is the phototoxic and hepatotoxic substance accumulating in erythropoietic protoporphyria (EPP). It is built in the maturing red blood cells from two substrates, one of them the amino acid glycine. A new causative approach to treat EPP was published in March of this year by research groups based in Zurich and London. By screening existing pharmaceutical substances (so called “repurposing”) they were able to identify two candidate compounds with a potential useful application in EPP. For the screening, a genetically modified cell culture model was used that mimics EPP and accumulates high amounts of protoporphyrin. The candidate compounds inhibited the uptake of glycine into the cells and lowered their protoporphyrin content. The effect was also present when treating maturing red blood cells derived from an EPP patient. One of the substances, bitopertin, was originally developed by Roche and has been tested in clinical trials with collectively more than 4000 health volunteers and patients with other conditions, where it was shown to be safe for the use in humans. Disc Medicine, a US based biotech company, recently acquired the licence from Roche to further develop bitopertin and announced a phase II clinical trial in patients with EPP, planned for 2022. We are excited to see results from basic research being taken up by industry this rapidly. If successful, the porphyria community could soon witness the development of the first causative treatment option for EPP and other erythropoietic porphyrias.
