Fanconi anemia future or investigational therapies: Difference between revisions
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'''Therapies under development''' | '''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.<ref name="pmid28801449">{{cite journal| author=Río P, Navarro S, Guenechea G, Sánchez-Domínguez R, Lamana ML, Yañez R et al.| title=Engraftment and in vivo proliferation advantage of gene-corrected mobilized CD34+ cells from Fanconi anemia patients. | journal=Blood | year= 2017 | volume= 130 | issue= 13 | pages= 1535-1542 | pmid=28801449 | doi=10.1182/blood-2017-03-774174 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28801449 }}</ref><blockquote>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.<ref name="pmid4685155">{{cite journal| author=Arefolov VA, Raevskiĭ KS| title=[Electron microscopic study of the effect of triftazin on reticular formation neurons in the rat medulla oblongata and mesencephalon]. | journal=Farmakol Toksikol | year= 1973 | volume= 36 | issue= 1 | pages= 5-8 | pmid=4685155 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4685155 }}</ref></blockquote> | ● '''[[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.<ref name="pmid28801449">{{cite journal| author=Río P, Navarro S, Guenechea G, Sánchez-Domínguez R, Lamana ML, Yañez R et al.| title=Engraftment and in vivo proliferation advantage of gene-corrected mobilized CD34+ cells from Fanconi anemia patients. | journal=Blood | year= 2017 | volume= 130 | issue= 13 | pages= 1535-1542 | pmid=28801449 | doi=10.1182/blood-2017-03-774174 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28801449 }}</ref><blockquote>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.<ref name="pmid4685155">{{cite journal| author=Arefolov VA, Raevskiĭ KS| title=[Electron microscopic study of the effect of triftazin on reticular formation neurons in the rat medulla oblongata and mesencephalon]. | journal=Farmakol Toksikol | year= 1973 | volume= 36 | issue= 1 | pages= 5-8 | pmid=4685155 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=4685155 }}</ref></blockquote> | ||
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| colspan="1" rowspan="1" |Inclusion Criteria | | colspan="1" rowspan="1" |Inclusion Criteria | ||
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| colspan="1" rowspan="1" |2. Patients with an HLA identical sibling donor. | | colspan="1" rowspan="1" |2. Patients with an HLA identical sibling donor. | ||
|} | |} | ||
● | ● [[Metformin]] – In a mouse model of FA (''FANCD''2 gene knockout), metformin produced modest increases in white blood cell (WBC) counts, hemoglobin levels, and platelet counts.<ref name="pmid27756748">{{cite journal| author=Zhang QS, Tang W, Deater M, Phan N, Marcogliese AN, Li H et al.| title=Metformin improves defective hematopoiesis and delays tumor formation in Fanconi anemia mice. | journal=Blood | year= 2016 | volume= 128 | issue= 24 | pages= 2774-2784 | pmid=27756748 | doi=10.1182/blood-2015-11-683490 | pmc=5159699 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27756748 }}</ref> 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. | ||
__NOTOC__ | __NOTOC__ | ||
Latest revision as of 18:11, 26 June 2018
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.
References
- ↑ 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.
- ↑ 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.
- ↑ 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.