The evaluation of candidate therapeutic agents for the treatment of bone marrow failure in patients with Fanconi anemia (FA) is constrained by several challenges including the disease heterogeneity and the limited number of primary human hematopoietic cells available to study. In vitro assays of human hematopoiesis do not provide information about the correction of long- term multilineage hematopoiesis, a critical endpoint that determines the efficacy of therapy for bone marrow failure in FA and related disorders. The predictive value of preclinical studies can be significantly enhanced by the use of robust in vivo modelling. We have developed a novel, double-chimeric xenograft model that allows us for the first time to rigorously test candidate therapeutic agents for their potential to correct steady-state human FA deficient hematopoiesis. The goal of this Xenograft Core is to fully evaluate the acute and chronic effects of the administration of lead therapeutic compounds identified in Projects 1 & 2 of this proposal.
The goal of the Xenograft Core is to evaluate the efficacy of candidate therapeutic agents in Fanconi anemia. Lead compounds identified in Projects 1 & 2 of this proposal will be tested an in vivo model to determine their potential to enhance both short-term and long-term hematopoiesis in human Fanconi A deficiency.
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