Fanconi’s anemia is a rare genetic disease that affects the repair of DNA. It is characterized in particular by variable congenital malformations, progressive medullary aplasia and a high risk of developing certain cancers.
What is Fanconi’s anemia?
Fanconi’s anemia is a rare genetic disease that belongs to hereditary medullary failure syndromes, dysfunctions affecting the production of blood stem cells in the bone marrow and affecting the stem cells in the blood, which leads to congenital anomalies and to predisposition to certain cancers. It affects both sexes and it is often diagnosed late, at the stage at which medullary failure appears. Hematological progression leads to severe medullary aplasia or leukemia.
The mutation in the fanc-A gene is the one most frequently found in this pathology. The prevalence of type-A Fanconi’s anemia is estimated at around 1/200,000.
Hematopoietic cell transplant is today the only treatment, but this approach involves risks to patients sensitive to cellular stress. The risks are related to infections and secondary cancers, to the need to take immuno-suppressing drugs and the occurrence of severe complications such as graft vs. host disease (GvH). The occurrence of chronic GvH disease can cause the development of carcinoma in patients.
Fanconi’s anemia: Genethon’s role
Genethon was a partner of the European consortium Eurofancolen, which enabled the phase I/II clinical trial for gene therapy for type-A Fanconi’s anemia. The treatment involves the use of a lentiviral vector that was developed and produced at Genethon and Yposkesi, in collaboration with teams from Ciemat.
Fanconi’s anemia: what’s happening today?
The ongoing clinical trial in Madrid, carried out with the vector developed at Genethon, is continuing with a long-term follow-up study which is now underway.
Other gene therapy clinical trials with an improved protocol are being conducted by Rocket Pharma in the United States, the United Kingdom and Spain. In 2020, the first results on the first 7 patients treated in the US were reported at the ASH meeting and are encouraging. One patient even saw their blood count increase after 1 year of treatment.
Fanconi’s anemia: find out more
- Success of a gene therapy for Fanconi’s anemia (09/09/2019)
- Río, P., et al. (2019). Successful engraftment of gene-corrected hematopoietic stem cells in non-conditioned patients with Fanconi anemia. Nature Medicine 25(9): 1396-1401.
- Río, P., et al. (2017). Engraftment and in vivo proliferation advantage of gene-corrected mobilized CD34+ cells from Fanconi anemia patients. Blood 130(13): 1535-1542.
- Molina-Estevez, F. J., A. Nowrouzi, et al. (2015). Lentiviral-Mediated Gene Therapy in Fanconi Anemia-A Mice Reveals Long-Term Engraftment and Continuous Turnover of Corrected HSCs. Curr Gene Ther 15(6): 550-562.