Osteopetrosis rescue upon RANKL administration to Rankl(-/-) mice : a new therapy for human RANKL-dependent ARO
Articolo
Data di Pubblicazione:
2012
Citazione:
Osteopetrosis rescue upon RANKL administration to Rankl(-/-) mice : a new therapy for human RANKL-dependent ARO / N. Lo Iacono, H.C. Blair, P.L. Poliani, V. Marrella, F. Ficara, B. Cassani, F. Facchetti, E. Fontana, M.M. Guerrini, E. Traggiai, F. Schena, M. Paulis, S. Mantero, A. Inforzato, S. Valaperta, A. Pangrazio, L. Crisafulli, V. Maina, P. Kostenuik, P. Vezzoni, A. Villa, C. Sobacchi. - In: JOURNAL OF BONE AND MINERAL RESEARCH. - ISSN 0884-0431. - 27:12(2012 Dec), pp. 2501-2510. [10.1002/jbmr.1712]
Abstract:
In the last decades the molecular basis of monogenic diseases has been largely unraveled, although their treatment has often remained
unsatisfactory. Autosomal recessive osteopetrosis (ARO) belongs to the small group of genetic diseases that are usually treated with
hematopoietic stem cell transplantation (HSCT). However, this approach is not effective in the recently identified form carrying mutations
in the receptor activator of NF-kB ligand (RANKL) gene. In this subset, therapy replacement approach based on RANKL delivery has a
strong rationale. Here we demonstrate that the systematic administration of RANKL for 1 month to Rankl-/- mice, which closely
resemble the human disease, significantly improves the bone phenotype and has beneficial effects on bone marrow, spleen and thymus;
major adverse effects arise only when mice are clearly overtreated. Overall, we provide evidence that the pharmacological administration
of RANKL represents the appropriate treatment option for RANKL-deficient ARO patients, to be validated in a pilot clinical trial.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
BONE; OSTEOPETROSIS; RANKL; THERAPY; HEMATOLYMPHOID COMPARTMENT
Elenco autori:
N. Lo Iacono, H.C. Blair, P.L. Poliani, V. Marrella, F. Ficara, B. Cassani, F. Facchetti, E. Fontana, M.M. Guerrini, E. Traggiai, F. Schena, M. Paulis, S. Mantero, A. Inforzato, S. Valaperta, A. Pangrazio, L. Crisafulli, V. Maina, P. Kostenuik, P. Vezzoni, A. Villa, C. Sobacchi
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