Clinical research Unit

Research activity

Hematopoietic stem cell gene therapy (HSC-GT) has become an attractive therapeutic strategy for inherited genetic disorders, offering several potential advantages over allogeneic HSC transplantation. Since 2000, SR-Tiget has successfully treated with ex vivo HSC gene therapy more than 120 patients affected by Adenosine Deaminase-Severe Combined Immunodeficiency (ADA-SCID), Wiskott-Aldrich Syndrome (WAS), Metachromatic Leukodystrophy (MLD), β-Thalassemia (BTHAL) and Mucopolysaccharidosis Type I Hurler (MPSIH).


SR-Tiget pioneered the gene therapy of ADA-SCID, a severe primary immunodeficiency, developing an HSC-based gene therapy employing ɣ-retroviral vectors. Thanks to a strategic collaboration formed in 2010 between Fondazione Telethon, Ospedale San Raffaele and GlaxoSmithKline, the treatment was registered and is available on the EU market since 2016.


The successful results obtained with ADA-SCID provided a rationale for extending the HSC gene therapy approach to other diseases, employing the more advanced lentiviral vector platform. In particular, two clinical trials for WAS and MLD, started in 2010, have completed the treatment phase and are showing evidence of persistent and clear therapeutic benefits in all treated patients. The Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) has given in 2020 marketing authorization of the gene therapy for the treatment of MLD.


A third HSC gene therapy clinical trial with lentiviral vectors for BTHAL, started in 2015, has provided evidence of safety and efficacy in the first nine patients. In addition, in 2018 we initiated a first‐in‐human clinical trial of LV-based HSC-gene therapy for MPSIH, which is already showing promising preliminary results.


The main goals of the Unit are the following:

  1. Broadening the target diseases of HSC-GT from SR-Tiget development pipeline to include other conditions
  2. Address ways to ease the regulatory burden of clinical testing of novel Advanced Therapy Medicinal Products by enabling am innovative platform-based approach in paradigmatic case studies
  3. Contribute to further clinical development and market access to patients of externally licensed product
  4. Bring to clinical application new platforms ex vivo gene editing and in vivo LV delivery

In addition, the following aims represent common objectives across the different trials:

  • to study the biological activity, clinical safety and efficacy of HSC gene therapy protocols, investigating the correction of disease features and key parameters determining the outcome of the treatment (e.g. genotype/phenotype, disease status at treatment, HSC cell dose and source, actual exposure to conditioning);
  • to inform basic research by contributing to the investigation of disease pathogenesis (natural history studies, identification of biomarkers), and to the characterization of the biological properties of HSC through the study of hematopoietic reconstitution after stem cell transplantation.