Susana Navarro Ordóñez

Susana Navarro has been working on the development and improvement of Gene Therapy for rare diseases focused in anemias and bone marrow failure syndromes such as porphyrias, Fanconi Anemia (FA) and Pyruvate kinase Deficiency (PKD) since more than 20 years. In 2003 she joined the Division and Innovative Therapies of the Hematopoietic System at CIEMAT/CIBERER/IIS-FJD and she was involved in the study of animal models for both FA and PKD and in the follow up uf bone marrow samples from FA and PKD and the development of transduction protocols to restore the hematological clinical manisfestations of both diseases. She has participated in lentiviral mediated gene therapy for FA and PKD since the beguining of these nowadays clinical programns; being involved in the generation of 4 Orphan Drug Designations (ODD) based on lentiviral gene therapy products first for the treatment of FA  ( EMA/COMP/662962/2010 and #DRU-2016-5193) and PKD ( EMA/COMP/865665/2014 and DRU-2016-5168) both in Europe and the USA, the presentation of IMPD/INDs, manufacturing of the medicinal product as Supervisor of the Clinistem GMP facility at the CIEMAT and follow up for the subsequent Phase I/II gene therapy trials on these diseases, currently on going under the Sponsor of the company Rocket Pharmaceuticals.

Aditionally during some year she intended to new sources of hematopoietic cells, workinh in the generation of iPSCs and in the differentiation of these to hematopoietic progenitors, as well as in the development of new gene therapy strategies working in the field of gene editing.

Due to this expertise she´s currently cordinating a gene therapy program in Diamond Blacfan anemia, developing different non-targeted and targeted gene therapy aproaches to restore the hematopoietic clinical signs of DBA patients. Recently, the preclinical resulst obtained in this respect have allowed the designation of this strategy as an orphan medicinal product for the treatment of Diamond-Blackfan anemia by the European Medicaments Agency (EMA/OD/0000060407). In relation with this program she´s currently co-cordinating a European Project from EJPRD in gene therapy for Blackfan Diamond anemia with a permanent position as “Investigador Científico de OPIS at CIEMAT”.

Publications:

1: Casado JA, Valeri A, Sanchez-Domínguez R, Vela P, Lopez A, Navarro S, Alberquilla O, Hanenberg H, Pujol R, Segovia JC, Minguillón J, Surrallés J, Diaz-de-Heredia C, Sevilla J, Rio P, Bueren JA. Upregulation of NKG2D ligands impairs hematopoietic stem cell function in Fanconi anemia. J Clin Invest. 2022 Jun 7:e142842. doi: 10.1172/JCI142842. Epub ahead of print. PMID: 35671096.

2: Navarro S, Quintana-Bustamante O, Sanchez-Dominguez R, Lopez-Manzaneda S, Ojeda-Perez I, Garcia-Torralba A, Alberquilla O, Law K, Beard BC, Bastone A, Rothe M, Villanueva M, Ramirez JC, Fañanas-Baquero S, Nieto-Romero V, Molinos- Vicente A, Gutierrez S, Nicoletti E, García-Bravo M, Bueren JA, Schwartz JD, Segovia JC. Preclinical studies of efficacy thresholds and tolerability of a clinically ready lentiviral vector for pyruvate kinase deficiency treatment. Mol Ther Methods Clin Dev. 2021 Jul 29;22:350-359. doi: 10.1016/j.omtm.2021.07.006. PMID: 34514027; PMCID: PMC8408550.

3: Sevilla J, Navarro S, Rio P, Sánchez-Domínguez R, Zubicaray J, Gálvez E, Merino E, Sebastián E, Azqueta C, Casado JA, Segovia JC, Alberquilla O, Bogliolo M, Román-Rodríguez FJ, Giménez Y, Larcher L, Salgado R, Pujol RM, Hladun R, Castillo A, Soulier J, Querol S, Fernández J, Schwartz J, García de Andoín N, López R, Catalá A, Surralles J, Díaz-de-Heredia C, Bueren JA. Improved collection of hematopoietic stem cells and progenitors from Fanconi anemia patients for gene therapy purposes. Mol Ther Methods Clin Dev. 2021 Jun 12;22:66-75. doi: 10.1016/j.omtm.2021.06.001. PMID: 34485595; PMCID: PMC8390450.

4: Ramírez MJ, Pujol R, Trujillo-Quintero JP, Minguillón J, Bogliolo M, Río P, Navarro S, Casado JA, Badell I, Carrasco E, Balmaña J, Català A, Sevilla J, Beléndez C, Argilés B, López M, Díaz de Heredia C, Rao G, Nicoletti E, Schwartz JD, Bueren JA, Surrallés J. Natural gene therapy by reverse mosaicism leads to improved hematology in Fanconi anemia patients. Am J Hematol. 2021 Aug 1;96(8):989-999. doi: 10.1002/ajh.26234. Epub 2021 May 25. PMID: 33984160.

5: Pino-Barrio MJ, Giménez Y, Villanueva M, Hildenbeutel M, Sánchez-Dominguez R, Rodríguez-Perales S, Pujol R, Surrallés J, Río P, Cathomen T, Mussolino C, Bueren JA, Navarro S. TALEN mediated gene editing in a mouse model of Fanconi anemia. Sci Rep. 2020 Apr 24;10(1):6997. doi: 10.1038/s41598-020-63971-z. PMID: 32332829; PMCID: PMC7181878.

6: Nicoletti E, Rao G, Bueren JA, Río P, Navarro S, Surrallés J, Choi G, Schwartz JD. Mosaicism in Fanconi anemia: concise review and evaluation of published cases with focus on clinical course of blood count normalization. Ann Hematol. 2020 May;99(5):913-924. doi: 10.1007/s00277-020-03954-2. Epub 2020 Feb 17. PMID: 32065290; PMCID: PMC7196946.

7: Río P, Navarro S, Wang W, Sánchez-Domínguez R, Pujol RM, Segovia JC, Bogliolo M, Merino E, Wu N, Salgado R, Lamana ML, Yañez RM, Casado JA, Giménez Y, Román- Rodríguez FJ, Álvarez L, Alberquilla O, Raimbault A, Guenechea G, Lozano ML, Cerrato L, Hernando M, Gálvez E, Hladun R, Giralt I, Barquinero J, Galy A, García de Andoín N, López R, Catalá A, Schwartz JD, Surrallés J, Soulier J, Schmidt M, Díaz de Heredia C, Sevilla J, Bueren JA. Successful engraftment of gene-corrected hematopoietic stem cells in non-conditioned patients with Fanconi anemia. Nat Med. 2019 Sep;25(9):1396-1401. doi: 10.1038/s41591-019-0550-z. Epub 2019 Sep 9. PMID: 31501599.

8: Río P, Navarro S, Bueren JA. Advances in Gene Therapy for Fanconi Anemia. Hum Gene Ther. 2018 Oct;29(10):1114-1123. doi: 10.1089/hum.2018.124. PMID: 30117331.

9: 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. Engraftment and in vivo proliferation advantage of gene-corrected mobilized CD34+ cells from Fanconi anemia patients. Blood. 2017 Sep 28;130(13):1535-1542. doi: 10.1182/blood-2017-03-774174. Epub 2017 Aug 11. PMID: 28801449.

10: Navarro S, Giorgetti A, Raya A, Tolar J. Induced Pluripotency and Gene Editing in Fanconi Anemia. Curr Gene Ther. 2017;16(5):321-328. doi: 10.2174/1566523217666170118112050. PMID: 28103772.