San Raffaele Telethon Institute for Gene Therapy

Clinical research Unit

Head of Unit

Alessandro Aiuti

CSQ-IQNet_EN

The SR‐Tiget Clinical Research Unit (CRU) was established in 1999 to create an infrastructure with dedicated staff and in‐house expertise for conducting advanced therapies clinical trials for genetic diseases according to Good Clinical Practices (GCP) standards. The Unit was originally established through a dedicated grant of Fondazione Telethon to SR‐Tiget and is led by Alessandro Aiuti.

The mission of the CRU is the application of research discoveries and novel gene and cell therapy approaches to the treatment of genetic diseases focusing on primary immunodeficiencies, lysosomal storage disorders and hemoglobinopathies. It provides a suitable environment to translate the results of basic and clinical research into clinical practice and vice versa, while maintaining high quality standards of clinical trials. The CRU has been recognized as a center of excellence for the treatment of patients affected by genetic disorders, coming from various countries.

Advanced search >

Organization

The Unit is composed by a Clinical Hematology Research Unit and a Pediatric Clinical Research Unit. The activity of the Unit is supported by the SR-Tiget Clinical Trial Office, the SR-Tiget Clinical Lab and the “Just like home” program dedicated to patients and their families. All together the staff of the CRU has the required expertise for carrying out in-house advanced therapies-based clinical trials according to GCP. The CRU acts in strict cooperation with the Pediatric Immuno‐Hematology Unit of Ospedale San Raffaele and the San Raffaele Stem Cell Program:

The Pediatric Immuno-Hematology Unit, directed by Alessandro Aiuti, takes care of the diagnosis and treatment of pediatric patients affected by hematological, immunological and metabolic diseases, with a particular focus on genetic disorders;
The San Raffaele Stem Cell Program, directed by Fabio Ciceri, is the largest Italian hematopoietic stem cell transplant center. Special areas of interest are stem cell transplantation, cell and gene therapy and high-risk hematological malignancies.

The approach to the patients is holistic, taking care of all the medical, nursing and psychological aspects thanks to a multidisciplinary team.

Research activity

Clinical research activities aim at facilitating clinical translation of basic science and platform innovations deriving from SR-Tiget experimental research programs into novel experimental protocols for the treatment of inherited immunodeficiencies (Adenosine Deaminase-Severe Combined Immunodeficiency and Wiskott-Aldrich Syndrome), hematological diseases (β-thalassemia) and lysosomal storage disorders (Metachromatic Leukodystrophy and Mucopolysaccharidosis Type I Hurler). In addition, the Unit is performing clinical research to improve the knowledge of rare genetic diseases. SR-Tiget has implemented several successful gene therapy clinical trials, which have already treated >120 patients and led to the filing and approval of 2 novel advanced therapy medicines (out of the 11 gene therapy drugs approved in total in the European Union).

For more detailed information about research activity of Clinical research Unit click here.

Accreditation

The CRU and its cooperating Units obtained different accreditations, ensuring high quality standards of their activities:

ISO 9001 certification for Pediatric Immuno–Hematology Unit, Hematology and Bone Marrow Transplant Unit and SR-TIGET Clinical Trial office;
AIFA self-certification for conduction of Phase I Clinical Trials (Unità di Fase I);
JACIE certification for the Stem Cell Program European Blood and Marrow Transplantation group (EBMT);
Gruppo Italiano Trapianto Midollo Osseo (GITMO)/Centro Nazionale Trapianti (CNT);
European Reference Network_Rare Immunodeficiency, autoinflammatory and autoimmune disease Network (ERN-RITA)
Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP);

The Unit participates to the scientific activity of: Società Italiana di Pediatria, Società Italiana di Ematologia, Inborn Errors Working Party of EBMT, American Society of Hematology (ASH), American Society of Gene Therapy (ASGCT), European Society of Cell and Gene Therapy (ESGCT).

Selected publications

ADA-SCID

Aiuti A, Roncarolo MG, Naldini L. Gene therapy for ADA-SCID, the first marketing approval of an ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products. EMBO Mol Med. 2017 Jun; 9(6): 737–740.

Cicalese MP, Ferrua F, Castagnaro L, Pajno R, Barzaghi F, Giannelli S, Dionisio F, Brigida I, Bonopane M, Casiraghi M, Tabucchi A, Carlucci F, Grunebaum E, Adeli M, Bredius RG, Puck JM, Stepensky P, Tezcan I, Rolfe K, De Boever E, Reinhardt RR, Appleby J, Ciceri F, Roncarolo MG, Aiuti A. Update on the safety and efficacy of retroviral gene therapy for immunodeficiency due to adenosine deaminase deficiency. Blood. 2016. 128: 45-54.

Aiuti A, Cattaneo F, Galimberti S, Benninghoff U, Cassani B, Callegaro L, Scaramuzza S, Andolfi G, Mirolo M, Brigida I, Tabucchi A, Carlucci F, Eibl M, Aker M, Slavin S, Al-Mousa H, Al Ghonaium A, Ferster A, Duppenthaler A, Notarangelo L, Wintergerst U, Buckley RH, Bregni M, Marktel S, Valsecchi MG, Rossi P, Ciceri F, Miniero R, Bordignon C, Roncarolo MG. Gene Therapy for Immunodeficiency due to adenosine deaminase deficiency. N Engl J Med. 2009 Jan 29;360(5):447-58.

MLD

Fumagalli F, Calbi V, Natali Sora MG, Sessa M, Baldoli C, Rancoita PMV, Ciotti F, Sarzana M, Fraschini M, Zambon AA, Acquati S, Redaelli D, Attanasio V, Miglietta S, De Mattia F, Barzaghi F, Ferrua F, Migliavacca M, Tucci F, Gallo V, Del Carro U, Canale S, Spiga I, Lorioli L, Recupero S, Fratini ES, Morena F, Silvani P, Calvi MR, Facchini M, Locatelli S, Corti A, Zancan S, Antonioli G, Farinelli G, Gabaldo M, Garcia-Segovia J, Schwab LC, Downey GF, Filippi M, Cicalese MP, Martino S, Di Serio C, Ciceri F, Bernardo ME, Naldini L, Biffi A, Aiuti A. Lentiviral haematopoietic stem-cell gene therapy for early-onset metachromatic leukodystrophy: long-term results from a non-randomised, open-label, phase 1/2 trial and expanded access, Lancet 2022 Jan 22;399(10322):372-383.

Fumagalli F., Zambon A.A., Rancoita P.M.V., Baldoli C., Canale S., Spiga I., Medaglini S., Penati R., Facchini M,. Ciotti F., Sarzana M., Lorioli L., Cesani M., Natali Sora M.G., Del Carro U., Cugnata F., Antonioli G., Recupero S., Calbi V., Di Serio C., Aiuti A., Biffi A., and Sessa M. (2021). Metachromatic leukodystrophy: A single-center longitudinal study of 45 patients. J Inherit Metab Dis. 2021 Apr 15.

Sessa M, Lorioli L, Fumagalli , Acquati S, Redaelli D, Baldoli C, Canale S, Lopez ID, Morena F, Calabria A, Fiori R, Silvani P, Rancoita PM, Gabaldo M, Benedicenti F, Antonioli G, Assanelli A, Cicalese MP, Del Carro U, Sora MG, Martino S, Quattrini A, Montini E, Di Serio C, Ciceri F, Roncarolo MG, Aiuti A, Naldini L, Biffi A. Lentiviral haemopoietic stem-cell gene therapy in early-onset metachromatic leukodystrophy: an ad-hoc analysis of a non-randomised, open-label, phase 1/2 trial. Lancet 2016 Jul 30;388(10043):476-87.

Biffi A, Montini E, Lorioli L, Cesani M, Fumagalli F, Plati T, Baldoli C, Martino S, Calabria A, Canale S, Benedicenti F, Vallanti G, Biasco L, Leo S, Kabbara N, Zanetti G, Rizzo WB, Mehta NA, Cicalese MP, Casiraghi M, Boelens JJ, Del Carro U, Dow DJ, Schmidt M, Assanelli A, Neduva V, Di Serio C, Stupka E, Gardner J, von Kalle C, Bordignon C, Ciceri F, Rovelli A, Roncarolo MG, Aiuti A, Sessa M, Naldini L. Lentiviral hematopoietic stem cell gene therapy benefits metachromatic leukodystrophy. Science 2013 Aug 23;341(6148):1233158.

WAS

Consiglieri G, Ferrua F; San Raffaele Hospital Consortium, Aiuti A, Cicalese MP. A Case of Two Adult Brothers with Wiskott-Aldrich Syndrome, One Treated with Gene Therapy and One with HLA-Identical Hematopoietic Stem Cell Transplantation.J Clin Immunol. 2021 Nov 4. doi: 10.1007/s10875-021-01157-6.

Ferrua F, Cicalese MP, Galimberti S, Giannelli S, Dionisio F, Barzaghi F, Migliavacca M, Bernardo ME, Calbi V, Assanelli AA, Facchini M, Fossati C, Albertazzi E, Scaramuzza S, Brigida I, Scala S, Basso-Ricci L, Pajno R, Casiraghi M, Canarutto D, Salerio FA, Albert MH, Bartoli A, Wolf HM, Fiori R, Silvani P, Gattillo S, Villa A, Biasco L, Dott C, Culme-Seymour EJ, van Rossem K, Atkinson G, Valsecchi MG, Roncarolo MG, Ciceri F, Naldini L, Aiuti A. Lentiviral haemopoietic stem/progenitor cell gene therapy for treatment of Wiskott-Aldrich syndrome: interim results of a non-randomised, open-label, phase 1/2 clinical study. Lancet Haematol. 2019 May;6(5):e239-e253

Aiuti A, Biasco L, Scaramuzza S, Ferrua F, Cicalese MP, Baricordi C, Dionisio F, Calabria A, Giannelli S, Castiello MC, Bosticardo M, Evangelio C, Assanelli A, Casiraghi M, Di Nunzio S, Callegaro L, Benati C, Rizzardi P, Pellin D, Di Serio C, Schmidt M, Von Kalle C, Gardner J, Mehta N, Neduva V, Dow DJ, Galy A, Miniero R, Finocchi A, Metin A, Banerjee PP, Orange JS, Galimberti S, Valsecchi MG, Biffi A, Montini E, Villa A, Ciceri F, Roncarolo MG, Naldini L. Lentiviral hematopoietic stem cell gene therapy in patients with Wiskott-Aldrich syndrome. Science 2013 Aug 23;341(6148):1233151.

B-THAL

Marktel S, Scaramuzza S, Cicalese MP, Giglio F, Galimberti S, Lidonnici MR, Calbi V, Assanelli A, Bernardo ME, Rossi C, Calabria A, Milani R, Gattillo S, Benedicenti F, Spinozzi G, Aprile A, Bergami A, Casiraghi M, Consiglieri G, Masera N, D'Angelo E, Mirra N, Origa R, Tartaglione I, Perrotta S, Winter R, Coppola M, Viarengo G, Santoleri L, Graziadei G, Gabaldo M, Valsecchi MG, Montini E, Naldini L, Cappellini MD, Ciceri F, Aiuti A, Ferrari G. Intrabone hematopoietic stem cell gene therapy for adult and pediatric patients affected by transfusion-dependent ß-thalassemia.Nat Med. 2019 Feb;25(2):234-241

Marktel S, Cicalese MP, Giglio F, Scaramuzza S, Calbi V, Casiraghi M, Ciotti F, Lidonnici MR, Rossi C, Masera N, D'Angelo E, Mirra N, Origa R, Tartaglione I, Mandelli , Milani R, Gattillo S, Coppola M, Viarengo G, Santoleri L, Calabria A, Perrotta S, Montini E, Graziadei G, Naldini L, Cappellini MD, Ciceri F, Aiuti A, Ferrari G. Gene Therapy for Beta Thalassemia: Preliminary Results from the PHASE I/II Tiget-Bthal Trial of Autologous Hematopoietic Stem Cells Genetically Modified with GLOBE Lentiviral Vector. Blood 2017 130:355.

MPSIH

Gentner B, Tucci F, Galimberti S, Fumagalli F, De Pellegrin M, Silvani P, Camesasca C, Pontesilli S, Darin S, Ciotti F, Sarzana M, Consiglieri G, Filisetti C, Forni G, Passerini L, Tomasoni D, Cesana D, Calabria A, Spinozzi G, Cicalese MP, Calbi V, Migliavacca M, Barzaghi F, Ferrua F, Gallo V, Miglietta S, Zonari E, Cheruku PS, Forni C, Facchini M, Corti A, Gabaldo M, Zancan S, Gasperini S, Rovelli A, Boelens JJ, Jones SA, Wynn R, Baldoli C, Montini E, Gregori S, Ciceri F, Valsecchi MG, la Marca G, Parini R, Naldini L, Aiuti A, Bernardo ME; MPSI Study Group. Hematopoietic Stem- and Progenitor-Cell Gene Therapy for Hurler Syndrome. N Engl J Med. 2021 Nov 18;385(21):1929-1940. doi: 10.1056/NEJMoa2106596.

GENERAL TOPICS

Tucci F., Galimberti, Naldini L., Valsecchi MG, Aiuti A., Gene therapy with hematopoietic stem and progenitor cells for monogenic disorders: a systematic review and meta-analysis, submitted

Canarutto D., Tucci F., Gattillo S., Zambelli M., Calbi V., Gentner B. , Ferrua F., Marktel S., Migliavacca M.,Barzaghi F., Consiglieri G., Gallo V., Fumagalli F., Massariello P., Parisi C., Viarengo G., Albertazzi E., Silvani P.,Milani R., Santoleri L., Ciceri F., Cicalese M.P., Bernardo M.E., and Aiuti A. (2021). Peripheral blood stem and progenitor cell collection in pediatric candidates for ex vivo gene therapy: a 10 year series . Molecular Therapy: Methods & Clinical Development. Mol Ther Methods Clin Dev 2021 Jun 1;22:76-83.