1. Early skeletal outcomes after hematopoietic stem and progenitor cell gene therapy for Hurler syndrome
- Author
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Consiglieri, G, Tucci, F, De Pellegrin, M, Guerrini, B, Cattoni, A, Risca, G, Scarparo, S, Sarzana, M, Pontesilli, S, Mellone, R, Gasperini, S, Galimberti, S, Silvani, P, Filisetti, C, Darin, S, Forni, G, Miglietta, S, Santi, L, Facchini, M, Corti, A, Fumagalli, F, Cicalese, M, Calbi, V, Migliavacca, M, Barzaghi, F, Ferrua, F, Gallo, V, Recupero, S, Canarutto, D, Doglio, M, Tedesco, L, Volpi, N, Rovelli, A, la Marca, G, Valsecchi, M, Zancan, S, Ciceri, F, Naldini, L, Baldoli, C, Parini, R, Gentner, B, Aiuti, A, Bernardo, M, Consiglieri, Giulia, Tucci, Francesca, De Pellegrin, Maurizio, Guerrini, Barbara, Cattoni, Alessandro, Risca, Giulia, Scarparo, Stefano, Sarzana, Marina, Pontesilli, Silvia, Mellone, Renata, Gasperini, Serena, Galimberti, Stefania, Silvani, Paolo, Filisetti, Chiara, Darin, Silvia, Forni, Giulia, Miglietta, Simona, Santi, Ludovica, Facchini, Marcella, Corti, Ambra, Fumagalli, Francesca, Cicalese, Maria Pia, Calbi, Valeria, Migliavacca, Maddalena, Barzaghi, Federica, Ferrua, Francesca, Gallo, Vera, Recupero, Salvatore, Canarutto, Daniele, Doglio, Matteo, Tedesco, Lucia, Volpi, Nicola, Rovelli, Attilio, la Marca, Giancarlo, Valsecchi, Maria Grazia, Zancan, Stefano, Ciceri, Fabio, Naldini, Luigi, Baldoli, Cristina, Parini, Rossella, Gentner, Bernhard, Aiuti, Alessandro, Bernardo, Maria Ester, Consiglieri, G, Tucci, F, De Pellegrin, M, Guerrini, B, Cattoni, A, Risca, G, Scarparo, S, Sarzana, M, Pontesilli, S, Mellone, R, Gasperini, S, Galimberti, S, Silvani, P, Filisetti, C, Darin, S, Forni, G, Miglietta, S, Santi, L, Facchini, M, Corti, A, Fumagalli, F, Cicalese, M, Calbi, V, Migliavacca, M, Barzaghi, F, Ferrua, F, Gallo, V, Recupero, S, Canarutto, D, Doglio, M, Tedesco, L, Volpi, N, Rovelli, A, la Marca, G, Valsecchi, M, Zancan, S, Ciceri, F, Naldini, L, Baldoli, C, Parini, R, Gentner, B, Aiuti, A, Bernardo, M, Consiglieri, Giulia, Tucci, Francesca, De Pellegrin, Maurizio, Guerrini, Barbara, Cattoni, Alessandro, Risca, Giulia, Scarparo, Stefano, Sarzana, Marina, Pontesilli, Silvia, Mellone, Renata, Gasperini, Serena, Galimberti, Stefania, Silvani, Paolo, Filisetti, Chiara, Darin, Silvia, Forni, Giulia, Miglietta, Simona, Santi, Ludovica, Facchini, Marcella, Corti, Ambra, Fumagalli, Francesca, Cicalese, Maria Pia, Calbi, Valeria, Migliavacca, Maddalena, Barzaghi, Federica, Ferrua, Francesca, Gallo, Vera, Recupero, Salvatore, Canarutto, Daniele, Doglio, Matteo, Tedesco, Lucia, Volpi, Nicola, Rovelli, Attilio, la Marca, Giancarlo, Valsecchi, Maria Grazia, Zancan, Stefano, Ciceri, Fabio, Naldini, Luigi, Baldoli, Cristina, Parini, Rossella, Gentner, Bernhard, Aiuti, Alessandro, and Bernardo, Maria Ester
- Abstract
Mucopolysaccharidosis type I Hurler (MPSIH) is characterized by severe and progressive skeletal dysplasia that is not fully addressed by allogeneic hematopoietic stem cell transplantation (HSCT). Autologous hematopoietic stem progenitor cell-gene therapy (HSPC-GT) provides superior metabolic correction in patients with MPSIH compared with HSCT; however, its ability to affect skeletal manifestations is unknown. Eight patients with MPSIH (mean age at treatment: 1.9 years) received lentiviral-based HSPC-GT in a phase 1/2 clinical trial (NCT03488394). Clinical (growth, measures of kyphosis and genu velgum), functional (motor function, joint range of motion), and radiological [acetabular index (AI), migration percentage (MP) in hip x-rays and MRIs and spine MRI score] parameters of skeletal dysplasia were evaluated at baseline and multiple time points up to 4 years after treatment. Specific skeletal measures were retrospectively compared with an external cohort of HSCT-treated patients. At a median follow-up of 3.78 years after HSPC-GT, all patients treated with HSPC-GT exhibited longitudinal growth within WHO reference ranges and a median height gain greater than that observed in patients treated with HSCT after 3-year follow-up. Patients receiving HSPC-GT experienced complete and earlier normalization of joint mobility compared with patients treated with HSCT. Mean AI and MP showed progressive decreases after HSPC-GT, suggesting a reduction in acetabular dysplasia. Typical spine alterations measured through a spine MRI score stabilized after HSPC-GT. Clinical, functional, and radiological measures suggested an early beneficial effect of HSPC-GT on MPSIH-typical skeletal features. Longer follow-up is needed to draw definitive conclusions on HSPC-GT's impact on MPSIH skeletal dysplasia.
- Published
- 2024