GlaxoSmithKline PLC (GSK), Fondazione Telethon and Fondazione San Raffaele announced a new strategic alliance to research and develop novel treatments to address rare genetic disorders, using gene therapy carried out on stem cells taken from the patient’s bone marrow (ex vivo). The alliance capitalises on research performed at the San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET), a joint venture between Fondazione Telethon and Fondazione San Raffaele established since 1995.

Under the terms of the agreement, GSK will gain an exclusive licence to develop and commercialise an investigational gene therapy, for ADA Severe Combined Immune Deficiency (ADA-SCID) - a rare and life-threatening immune deficiency, which affects approximately 350 children worldwide. Phase-I/II studies have demonstrated the potential of this treatment option to restore long-term immune function and protect against severe infections in children with ADA deficiency.

In addition, GSK will co-develop with Fondazione Telethon and Fondazione San Raffaele, six further applications of ex vivo stem cell therapy, using a new gene transfer technology developed by HSR-TIGET scientists, with the potential to treat a range of rare disorders. This first of these will be metachromatic leukodystrophy (MLD) and Wiskott-Aldrich Syndrome (WAS). Others include; beta-thalassemia, mucopolysaccharoidosis type I (MPS); globoid leukodystrophy (GLD); and chronic granulomatous disorder (CGD). Clinical trials for WAS and MLD were initiated at HSR-TIGET last spring and are currently recruiting patients.

All of these disorders have a molecular mechanism that is well understood and are caused by faults in a single gene, making it possible for this ex vivo gene technology to correct the patient’s own bone marrow stem cells. When the treated stem cells are returned to the patient they express the corrected protein, providing an opportunity to treat the disease and side step much of the risk associated with immune-incompatibility that comes from stem cells supplied by a donor.

Fondazione Telethon will receive an upfront 10 million euro payment from GSK and is eligible to receive further payments upon successful completion of a number of predetermined development milestones.

“This alliance is an important addition to GSK’s growing portfolio in rare diseases and advances the work our stem cell researchers have been doing to deliver transformative regenerative therapies,” said Dr Philippe Monteyne, head of Development and chief medical officer for GSK Rare Diseases.  “Not only does the lead programme for ADA-SCID represent an opportunity to provide a treatment option for an under-served patient population, by combining our experience in manufacturing complex biological products with the pioneering research of world-leaders in gene and stem cell therapies, we have the chance to dramatically advance this field.”

“This collaboration is a breakthrough for gene therapy in rare diseases,” said professor Luigi Naldini, director of HSR-TIGET. “We have spent years researching these promising new technologies, but without GSK’s experience in developing medicines, we would not be able to take all the steps towards making a potential therapy available to patients.”

“This day is one of extraordinary importance for us,” said Francesca Pasinelli, general manager of Fondazione Telethon. “Through the years we have been raising donations with the promise of advancing towards the cure of rare genetic diseases. With this alliance we can show that the excellent scientific research we have funded could actually lead to viable therapies available to all patients.”

"San Raffaele and Telethon have a shared ambition to translate basic discoveries in the field of molecular medicine into treatments for patients," said Maria Grazia Roncarolo, scientific director of the San Raffaele Scientific Institute.  "We are really excited by the alliance with GSK, because we can now progress our research and know-how into potential treatments."

Fondazione Telethon is one of the biggest biomedical charities in Italy, whose mission is to advance biomedical research towards diagnosis, cure and prevention of genetic diseases.