Fanconi Anemia is a rare genetic disease in the category of bone marrow failure syndromes affecting blood stem cells and leading to bone marrow failure, congenital abnormalities and a predisposition to cancer.
It affects both sexes and is often diagnosed late, at the stage of onset of bone marrow failure. Patients develop hematological problems such as severe bone marrow aplasia or leukemia.
Fanc-A gene mutation is the most common mutation observed in this disease. The prevalence of Fanconi anemia type A is estimated to be about 1/200,000.
Hematopoietic cell transplantation is the only treatment available today, but this type of treatment is risky in these patients who are sensitive to cellular stress. The risks are related to infections and secondary cancers, the taking of immunosuppressive drugs and the appearance of serious complications such as graft-versus-host disease (GVH). The onset of chronic GvH can cause carcinomas to develop in these patients.
Genethon is a partner of the European consortium Eurofancolen, which has enabled the completion of a phase I / II clinical trial for the gene therapy of Fanconi anemia type A.
The clinical trial takes place in Madrid, Spain. The treatment is based on the use of a lentiviral vector that was developed and produced at Genethon in collaboration with Ciemat teams.
The vector is used to transduce blood stem cells. Dr. Juan Bueren recently presented the results of the treatment of the first five patients. The results are very encouraging, showing that it is possible, for the first time, to obtain engraftment of autologous blood stem cells corrected in these patients. The corrected cells have a selective advantage and are permanently established in the blood of patients, despite the lack of prior conditioning.
- « Engraftment and in vivo proliferation advantage of gene-corrected mobilized CD34+ cells from Fanconi anemia patients.» Río P, Navarro S, Guenechea G, Sánchez-Domínguez R, Lamana ML, Yañez R, Casado JA, Mehta PA, Pujol MR, Surrallés J, Charrier S, Galy A, Segovia JC, Díaz de Heredia C, Sevilla J, Bueren JA. Blood. 2017 Sep 28;130(13):1535-1542. doi: 10.1182/blood-2017-03-774174. Epub 2017 Aug 11.
- « Lentiviral-Mediated Gene Therapy in Fanconi Anemia-A Mice Reveals Long-Term Engraftment and Continuous Turnover of Corrected HSCs. » Molina-Estevez FJ, Nowrouzi A, Lozano ML, Galy A, Charrier S, von Kalle C, Guenechea G, BuerenJA, Schmidt M. Curr Gene Ther. 2015;15(6):550-62. PMID: 26415575