Patients with mucopolysaccharidosis type I Hurler (MPSIH) experience multisystem clinical manifestations, which are only partially addressed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study evaluated outcomes from a lentiviral vector-mediated hematopoietic stem and progenitor cell-gene therapy (HSPC-GT) trial ( NCT03488394 ) in eight MPSIH patients followed up to 4 years post-treatment. Key findings included corneal clouding, hearing loss (HL), carpal tunnel syndrome (CTS), and cardiac evaluations. A retrospective comparison with an external cohort of nine MPSIH patients undergoing allo-HSCT was performed. All patients are alive at last follow-up, show stable engraftment without graft failure, insertional oncogenesis, or immune responses to the transgene. Notably, at last follow-up 3/8 HSPC-GT patients experienced corneal clouding resolution, while all allo-HSCT patients maintained moderate corneal clouding; 4/8 HSPC-GT patients showed normal hearing function at last follow-up due to improvement ( n = 3) or stabilization ( n = 1); 7/9 allo-HSCT patients had mild or moderate HL at baseline, while 2/9 showed moderate HL at last follow-up. No HSPC-GT patients required surgery for CTS developed after HSPC-GT, while 7/9 patients needed such surgery after allo-HSCT. No HSPC-GT patients developed severe cardiomyopathy or valvular disease, while in the HSCT cohort 4/9 patients experienced progression of valvular insufficiency although not requiring valve replacement. Our results indicate a favorable effect of HSPC-GT on MPSIH multisystemic manifestations up to 4 years after treatment; long-term, prospective comparative studies are warranted for definitive conclusions.
Non-neurological, non-skeletal outcomes after hematopoietic stem and progenitor cell-gene therapy (OTL-203) for Hurler syndrome / Tucci, F.; Uria Oficialdegui, M. L.; Consiglieri, G.; Cossutta, M.; Filisetti, C.; Fumagalli, F.; Butera, C.; Santangelo, R.; Colombo, M.; Manitto, M. P.; Stoppani, M.; Martina, E.; Dane, G.; Camesasca, C.; Risca, G.; De Pellegrin, M.; Scarparo, S.; Sarzana, M.; Puricelli, C.; Galimberti, S.; Darin, S.; Silvani, P.; Bonanomi, S.; Gasperini, S.; Naldini, L.; Gentner, B.; Parini, R.; Del Toro, M.; Diaz-de-Heredia, C.; Aiuti, A.; Bernardo, M. E.. - In: MOLECULAR THERAPY. - ISSN 1525-0016. - 34:1(2026), pp. 443-454. [10.1016/j.ymthe.2025.09.042]
Non-neurological, non-skeletal outcomes after hematopoietic stem and progenitor cell-gene therapy (OTL-203) for Hurler syndrome
Consiglieri G.;Filisetti C.;Santangelo R.;Naldini L.;Aiuti A.;Bernardo M. E.
2026-01-01
Abstract
Patients with mucopolysaccharidosis type I Hurler (MPSIH) experience multisystem clinical manifestations, which are only partially addressed by allogeneic hematopoietic stem cell transplantation (allo-HSCT). This study evaluated outcomes from a lentiviral vector-mediated hematopoietic stem and progenitor cell-gene therapy (HSPC-GT) trial ( NCT03488394 ) in eight MPSIH patients followed up to 4 years post-treatment. Key findings included corneal clouding, hearing loss (HL), carpal tunnel syndrome (CTS), and cardiac evaluations. A retrospective comparison with an external cohort of nine MPSIH patients undergoing allo-HSCT was performed. All patients are alive at last follow-up, show stable engraftment without graft failure, insertional oncogenesis, or immune responses to the transgene. Notably, at last follow-up 3/8 HSPC-GT patients experienced corneal clouding resolution, while all allo-HSCT patients maintained moderate corneal clouding; 4/8 HSPC-GT patients showed normal hearing function at last follow-up due to improvement ( n = 3) or stabilization ( n = 1); 7/9 allo-HSCT patients had mild or moderate HL at baseline, while 2/9 showed moderate HL at last follow-up. No HSPC-GT patients required surgery for CTS developed after HSPC-GT, while 7/9 patients needed such surgery after allo-HSCT. No HSPC-GT patients developed severe cardiomyopathy or valvular disease, while in the HSCT cohort 4/9 patients experienced progression of valvular insufficiency although not requiring valve replacement. Our results indicate a favorable effect of HSPC-GT on MPSIH multisystemic manifestations up to 4 years after treatment; long-term, prospective comparative studies are warranted for definitive conclusions.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
