| Title: |
PS1220 EX‐VIVO HEMATOPOIETIC STEM CELL GENE THERAPY (GT) FOR MUCOPOLYSACCHARIDOSIS TYPE I HURLER (MPSIH): PRELIMINARY RESULTS FROM A PHASE I/II CLINICAL STUDY |
| Authors: |
Bernardo, M.E.; Gentner, B.; Tucci, F.; Fumagalli, F.; Silvani, P.; Filisetti, C.; Redaelli, D.; Acquati, S.; Zonari, E.; Rovelli, A.; Parini, R.; La Marca, G.; Naldini, L.; Aiuti, A. |
| Source: |
HemaSphere ; volume 3, issue S1, page 556-557 ; ISSN 2572-9241 2572-9241 |
| Publisher Information: |
Wiley |
| Publication Year: |
2019 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Background: MPSIH is a lysosomal storage disease caused by α‐L‐iduronidase (IDUA) deficiency that is associated with progressive multisystem morbidity including neurodevelopmental deterioration and severe orthopedic manifestations, leading to death in early childhood. Current therapeutic strategies include enzyme replacement therapy and allogeneic hematopoietic stem cell transplantation (HSCT), which however show limitations in preventing neurodevelopmental and orthopedic complications. Transplantation of genetically‐engineered autologous hematopoietic stem and progenitor cells (HSPC) is an attractive treatment option for MPSIH thanks to the possibility to obtain supraphysiologic levels of the missing enzyme in the hematopoietic progeny, thus allowing for increased cross‐correction. Aims: We recently opened a phase I/II clinical trial (NCT03488394) in children affected by MPSIH aimed at evaluating safety, tolerability and efficacy of the transplantation of autologous, IDUA lentiviral (LV)‐transduced CD34 + cells in MPSIH patients undergoing myeloablative conditioning. Methods: The study foresees the enrollment of 6 patients who lack a non‐heterozygous HLA‐matched donor and display an IQ/DQ>70. Primary endpoints of safety include: overall survival, hematological engraftment and safety of drug product (DP) administration. Primary endpoint of efficacy is represented by IDUA activity in peripheral blood up to supraphysiologic levels at 1 year post‐gene therapy (GT). Treatment impact on nervous system, skeleton and other target organs is assessed by clinical and radiologic parameters, as well as by disease‐specific biomarkers. Results: By the submission deadline, two patients (24 and 14 months old) were treated and have a follow‐up of 7 and 1.5 months, respectively. Autologous HSPC were harvested after mobilization with G‐CSF and Plerixafor; the procedure was uneventful and resulted in cryopreserved DP of 24 and 14 million CD34+ cells/kg, respectively. Transduction efficiency in the drug products was above 80% ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1097/01.hs9.0000563164.44448.4c |
| DOI: |
10.1097/01.HS9.0000563164.44448.4c |
| Availability: |
http://dx.doi.org/10.1097/01.hs9.0000563164.44448.4c; https://onlinelibrary.wiley.com/doi/pdf/10.1097/01.HS9.0000563164.44448.4c |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| Accession Number: |
edsbas.E8AB448F |
| Database: |
BASE |