Fanconi anemia future or investigational therapies

Jump to navigation Jump to search

Therapies under development

● Gene therapy – Gene therapy has the potential to improve bone marrow function in individuals with FA since the origin of bone marrow failure is deficiency of an FA gene function. Gene-corrected CD34+ stem cells from FA patients have been engrafted in immune-deficient mice, but successful clinical applications of gene therapy for FA have not yet been demonstrated.[1]

Major inclusion and exclusion criteria for gene therapy in patients with biallelic FANCA germ-line mutations as proposed by International Fanconi Anemia Gene Therapy Working Group.[2]

Inclusion Criteria 1. FA demonstrated by a positive test for increased sensitivity to chromosomal breakage with MMC/DEB and determination of FA complementation group A by somatic cell hybrids, molecular characterization, western blot analysis, direct FANCA sequencing, or acquisition of mitomycin C resistance after in vitro transduction with a vector bearing the FANCA cDNA.
2. Bone Marrow analysis demonstrating normal karyotype.
Exclusion Criteria 1. Uncontrolled infection (viral, bacterial, or fungal).
2. Patients with an HLA identical sibling donor.

Metformin – In a mouse model of FA (FANCD2 gene knockout), metformin produced modest increases in white blood cell (WBC) counts, hemoglobin levels, and platelet counts.[3] There was also reduced p53-dependent tumor formation and a suggestion of decreased susceptibility to DNA damage. Metformin has not been evaluated in patients with FA.


  1. Río P, Navarro S, Guenechea G, Sánchez-Domínguez R, Lamana ML, Yañez R; et al. (2017). "Engraftment and in vivo proliferation advantage of gene-corrected mobilized CD34+ cells from Fanconi anemia patients". Blood. 130 (13): 1535–1542. doi:10.1182/blood-2017-03-774174. PMID 28801449.
  2. Arefolov VA, Raevskiĭ KS (1973). "[Electron microscopic study of the effect of triftazin on reticular formation neurons in the rat medulla oblongata and mesencephalon]". Farmakol Toksikol. 36 (1): 5–8. PMID 4685155.
  3. Zhang QS, Tang W, Deater M, Phan N, Marcogliese AN, Li H; et al. (2016). "Metformin improves defective hematopoiesis and delays tumor formation in Fanconi anemia mice". Blood. 128 (24): 2774–2784. doi:10.1182/blood-2015-11-683490. PMC 5159699. PMID 27756748.