Treatment of the underlying cause of erythropoietic protoporphyria\n(EPP) made a big leap forward, as reported by two groups of Swiss scientists\nbased in Zurich. In over 97 % of ferrochelatase-deficient EPP patients, misregulation\nof the “healthy” copy of the gene for ferrochelatase reduces the\noverall enzyme activity below a threshold that causes the phototoxic heme\nprecursor protoporphyrin IX to accumulate in the body (Gouya et al. 2002). Earlier\nresults by a French group of scientists from Paris demonstrated that the misregulation\ncan be reversed by treating cells of EPP patients grown in culture with short,\nspecific DNA strands, so called “splice switching oligonucleotides”,\nwhich favorably modulate the splicing process of the genetic intermediary,\ncalled \u201cmessenger RNA\u201d, responsible for the production of ferrochelatase (Oustric\net al. 2014). However, the main obstacle in treating EPP patients with these\nkinds of therapeutics was to deliver the compounds into the main site of\nprotoporphyrin IX production, the developing red blood cells located in the\nbone marrow. By changing the chemical composition of the splice switching\noligonucleotide and coupling it to molecules that facilitate uptake by the bone\nmarrow, the Swiss research groups could demonstrate delivery of the compounds\nto the bone marrow in an EPP mouse model. The mouse had been previously developed\nby the two groups and carries the same misregulation in the ferrochelatase gene\nas found in human EPP patients (Barman-Aks\u00f6zen et al. 2017). Importantly,\nhighly efficient correction of the misregulation of the ferrochelatase gene\ncould also be demonstrated in the red blood cells of the mouse model. The study\nis therefore a proof-of-concept for a new, causative treatment option for EPP,\nwhich one day could broaden the available therapeutic alternatives to address\nthis life-limiting condition.<\/p>\n\n\n\n
The project is a collaboration between the municipal hospital Zurich (Swiss center for expertise for porphyrias) and the Swiss Federal Institute of Technology in Zurich and funded by the Swiss National Science Foundation as part of a National Centre of Competence in Research (NCCR) grant.<\/p>\n\n\n\n