Successful therapeutic effect in a mouse model of erythropoietic protoporphyria by partial genetic correction and fluorescence-based selection of hematopoietic cells

Gene Therapy
A FontanellasH de Verneuil

Abstract

Erythropoietic protoporphyria is characterized clinically by skin photosensitivity and biochemically by a ferrochelatase deficiency resulting in an excessive accumulation of photoreactive protoporphyrin in erythrocytes, plasma and other organs. The availability of the Fech(m1Pas)/Fech(m1Pas) murine model allowed us to test a gene therapy protocol to correct the porphyric phenotype. Gene therapy was performed by ex vivo transfer of human ferrochelatase cDNA with a retroviral vector to deficient hematopoietic cells, followed by re-injection of the transduced cells with or without selection in the porphyric mouse. Genetically corrected cells were separated by FACS from deficient ones by the absence of fluorescence when illuminated under ultraviolet light. Five months after transplantation, the number of fluorescent erythrocytes decreased from 61% (EPP mice) to 19% for EPP mice engrafted with low fluorescent selected BM cells. Absence of skin photosensitivity was observed in mice with less than 20% of fluorescent RBC. A partial phenotypic correction was found for animals with 20 to 40% of fluorescent RBC. In conclusion, a partial correction of bone marrow cells is sufficient to reverse the porphyric phenotype and restore normal hem...Continue Reading

References

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Citations

Jul 8, 2008·Médecine sciences : M/S·Hubert de VerneuilFrançois Moreau-Gaudry
Mar 11, 2005·Journal of Clinical Gastroenterology·Joseph BloomerHiba Risheg
Dec 24, 2009·Transplantation·María García-BravoRafael Enríquez de Salamanca
Jan 18, 2005·Lancet·Raili Kauppinen
Aug 7, 2009·The Journal of Investigative Dermatology·Staffan Wahlin, Pauline Harper
Nov 30, 2005·Genomics·C GedH de Verneuil
Oct 11, 2001·Molecular Therapy : the Journal of the American Society of Gene Therapy·E RichardF Moreau-Gaudry
Jan 29, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·Marie AbitbolXavier Montagutelli
Jun 25, 2019·Clinical Genetics·Juan A BuerenGuillermo Guenechea
Dec 1, 2004·Photochemical & Photobiological Sciences : Official Journal of the European Photochemistry Association and the European Society for Photobiology·Lars KaestnerJohan Moan

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