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., et al.. - 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.
