Under development

An overview of therapies currently in development for different genetic diseases.

At Fondazione Telethon, we are pursuing different therapeutic strategies to address rare genetic diseases, including gene therapies (ex vivo and in vivo), gene editing approaches such as CRISPR-Cas9, and small-molecule treatments targeting disease mechanisms at the molecular level. 

These programs span various stages—from preclinical research to Phase I/II trials, and up to Phase III studies aimed at regulatory approval. Ownership models vary: some therapies are developed exclusively by Fondazione Telethon, others in partnership with academic or biotech entities, and some are licensed to external companies. 

Below is an overview of therapies currently in development for different genetic diseases:

A rare X-linked immunodeficiency caused by mutations in the WAS gene. It presents in early childhood with recurrent infections, eczema, bleeding, autoimmunity, and increased risk of lymphoma. The only potentially curative option is hematopoietic stem cell transplantation, for which a compatible donor is not always available, and which is not without risks. An ex vivo lentiviral gene therapy has been developed at SR-Tiget: it has been shown that reduces the frequency of severe and moderate bleeding events and serious infections in patients with WAS compared with the period prior to treatment. In cases where transplantation from a compatible family donor is not possible, gene therapy represents a potential therapeutic option for eligible patients. Fondazione Telethon has submitted a Marketing Authorization Application to the EMA, and a Biologics License Application to the FDA, to make this therapy available both in EU and US. 

A severe lysosomal storage disorder caused by deficiency of the IDUA enzyme, leading to skeletal abnormalities, neurocognitive decline, and multi-organ dysfunction. Without treatment, the disease is often fatal in childhood. The ex vivo hematopoietic stem cell gene therapy OTL-203, developed at SR-Tiget and licensed to Orchard Therapeutics, is under evaluation in the HURCULES Phase III trial. Earlier studies at Ospedale San Raffaele showed durable metabolic correction and motor and cognitive stabilization.  

A genetic blood disorder that causes severe anemia and usually requires lifelong transfusions. An ex vivo lentiviral gene therapy developed at SR-Tiget showed encouraging results in a Phase I/II trial: patients experienced reduced transfusion needs, and several children became transfusion independent. A new Phase II trial sponsored by Fondazione Telethon is planned for 2026 with Ospedale Pediatrico Bambino Gesù.  

An ultra-rare lysosomal disorder due to ARSB deficiency, causing skeletal dysplasia, corneal clouding, and cardiac involvement. A liver-directed in vivo AAV gene therapy developed by TIGEM scientists was tested in a Phase I/II trial in Naples and Ankara. Results published in 2022 showed sustained ARSB expression and encouraging clinical stabilization. An extension trial sponsored by Fondazione Telethon with a higher vector dose is planned for 2026. 

A rare primary immunodeficiency caused by mutations in the CD40LG gene, leading to recurrent infections, autoimmune complications, and reduced life expectancy. At SR-Tiget, a CRISPR-Cas9 gene editing approach has been developed to correct the CD40LG defect in hematopoietic stem cells and T cells. Preclinical studies showed restored antibody production and immune function. The first clinical trial in patients, sponsored by Fondazione Telethon and Ospedale San Raffaele, is expected in 2026. 

A severe metabolic disorder caused by mutations in the MUT gene, leading to toxic accumulation of methylmalonic acid and multi-organ damage. An in vivo gene therapy, developed by Genespire (a spin-off of SR-Tiget), uses immune-shielded lentiviral vectors to restore MUT activity in the liver. Preclinical studies showed durable metabolic correction in disease models. A Phase I/II trial, sponsored by Genespire, is in preparation. 

A disorder caused by mutations in the MYO7A gene, combining congenital deafness with progressive vision loss. The LUCE-1 Phase I/II trial is testing an AAV8-based gene therapy developed at TIGEM and licensed to AAVantgarde Bio, a spin-off of the Institute. The therapy uses a dual-vector platform to deliver large genes such as MYO7A via subretinal injection. The Phase I/II trial began in 2024, with the first patient dosed at the University of Campania “Luigi Vanvitelli”.  

A hereditary macular dystrophy caused by mutations in the ABCA4 gene, leading to progressive vision loss in children and young adults. AAVantgarde Bio is developing a dual AAV gene therapy delivering the full-length ABCA4 protein, based on the platform developed at TIGEM and licensed by Fondazione Telethon. The program has received FDA Fast Track designation, and the CELESTE Phase I/II trial is now underway. 

A group of ultra-rare lysosomal storage disorders that cause skeletal deformities, disability, and multi-organ complications. The PLATFORM project, developed at SR-Tiget, uses a shared ex vivo lentiviral gene therapy platform with common components (vector backbone, promoter, regulatory elements), modified only by the disease-specific transgene. This parallel strategy reduces time and costs across multiple conditions. Fondazione Telethon is working towards submitting a Phase I/II trial dossier in the coming years. 

A rare skeletal disease in which defective bone resorption leads to abnormal density and life-threatening complications in infancy. SR-Tiget has developed an ex vivo lentiviral gene therapy targeting hematopoietic stem cells. Following promising preclinical studies, a Phase I/II trial is planned to start in 2026, in collaboration with Ospedale San Raffaele. 

An X-linked condition characterized by congenital cataracts, kidney dysfunction with protein loss, and intellectual disability. No approved therapies exist. Based on preclinical evidence discovered ad TIGEM, Can-Fite BioPharma is sponsoring a Phase II open-label trial of Piclidenoson, an A₃ adenosine receptor agonist, at Bambino Gesù Children’s Hospital in Rome. 

A devastating childhood neurodegenerative disorder leading to progressive loss of cognitive and motor skills. TIGEM, supported by Fondazione Telethon, is developing a small-molecule therapy aimed at slowing disease progression. The project is currently in preclinical development. 

A lysosomal storage disorder caused by deficiency of the enzyme acid alpha-glucosidase (GAA), leading to glycogen accumulation in muscles, liver, nerves, and brain. While enzyme replacement therapy improves survival, it has limited impact on neurological complications. TIGEM, supported by Fondazione Telethon, is developing an in vivo gene therapy approach targeting the central nervous system to restore GAA activity in the brain. This approach aims to address neurological symptoms that remain untreated by current therapies. 

A prion disease caused by a mutation in the PRNP gene, leading to progressive insomnia, autonomic dysfunction, and cognitive decline. The disease is invariably fatal within a few years from onset. Fondazione Telethon is funding a Phase II preventive trial testing doxycycline in asymptomatic carriers. The study, led by the Mario Negri Institute, foresees 10 years of treatment with doxycycline versus placebo, with survival as the primary endpoint. 

A group of muscular dystrophies, including Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM), caused by mutations in COL6A1, COL6A2, or COL6A3. Preclinical studies supported by Fondazione Telethon at University of Padua, showed that cyclophilin D inhibition protects mitochondria and improves muscle function in collagen VI myopathy models. Based on this evidence, Fondazione Telethon will sponsor a Phase II trial of Alisporivir (Debio025), a drug owned by Debiopharm originally developed as an antiviral, to assess safety and preliminary efficacy in patients.