Fanconi anemia is a rare genetic disease characterized by early onset of bone marrow failure (BMF). Our group is currently developing lentiviral-mediated gene therapy approaches to correct the predisposition of BMF in these patients.
Thanks to previous studies we designed a therapeutic lentiviral vector and developed an improved transduction protocol that avoids the extended in vitro manipulation of hematopoietic stem cells collected from FA patients of the FA-A subtype.
Under the sponsorship of Hospital Val d’Hebrón a phase I/II clinical trial was developed to optimize the collection of HSCs from these patients (Conclusions are already published at Sevilla, Navarro, Rio, et al Mol. Ther. Meth. and Clinic Dev., 2021). Thereafter an innovative European Phase I/II clinical trial (FANCOLEN I) was developed, in which patients are treated in the absence of any conditioning. This trial was sponsored by Hospital del Niño Jesús, and has recently concluded the 3-year follow-up, showing for the first time the possibility of correcting BMF in patients with early engraftment of corrected cells ((see preliminary results at Rio et al. Nature Medicine, 2019).
Thanks to the licensing of the therapeutic lentiviral vector to Rocket Pharmaceuticals, Inc (Rocket), and also based on the initial results obtained in the Fancolen I trial, Rocket is currently sponsoring a long-term follow-up trial of patients treated in the FANCOLEN I study and has also opened a global Phase II trial for FA-A patients at early stages of the disease. In this new trial, CIEMAT actively participates in the patients’ screening, as well as in the manufacturing of corrected cells and in the follow up of the patients.
In a new collaboration with Rocket, we are currently conducting the preclinical studies to develop similar clinical trials in FA patients with mutations in FANCC and FANCG, that will facilitate to extend our safe gene therapy approach to around 90% of FA patients corresponding to the different subtypes worldwide.
