Viruses Treatment Articles

Gene Therapy For Rare Genetic Disorders, Glaxo And Two Italian Groups Form Alliance

April 30, 2017

GlaxoSmithKline, Fondazione San Raffaele and Fondazione Telethon have entered an alliance to develop gene therapies for rare genetic disorders. The therapies use stem cells taken from the patient's own bone marrow. Initially, GlaxoSmithKline (GSK) will have the exclusive license to develop and market an experimental gene therapy for ADA Severe Combined Immune Deficiency - a congenital disorder which leads to low levels of B and T cells in the child's immune system. About 350 children are affected with ADA Severe Combined Immune Deficiency (ADA-SCID) annually around the world. ADA-SCID is often referred to as "bubble boy disease". Children with SCID have an extremely high risk of severe infections, retarded growth and premature death.

Phase I and Phase II trials have shown promise for the treatment of ADA-SCID in restoring long-term immunity, as well as protecting against severe infections.

Along with Fondazione San Raffaele and Fondazione Telethon, GSK will co-develop six additional applications of ex vivo stem cell therapy (use stem cells taken from the patient's bone marrow), utilizing a novel gene transfer technology created by San Raffaele Telethon Institute for Gene Therapy (HSR-TIGET) researchers - their technology has enormous potential to treat a wide range of uncommon disorders, including: Metachromatic leukodystrophy (MLD) - clinical trials started in the Spring of 2010, still recruiting patients (18th October, 2010) Wiskott-Aldrich Syndrome (WAS) - clinical trials started in the Spring of 2010, still recruiting patients (18th October, 2010) Beta-thalassemia, mucopolysaccharoidosis type I (MPS) Globoid leukodystrophy (GLD) Chronic granulomatous disorder (CGD) All the above-mentioned disorders are caused by abnormalities in just one gene, meaning that ex vivo technology may correct the bone marrow stem cells of the patient. The molecular mechanism of these disorders is well understood. The stem cells are taken out, expressed with the corrected protein, and then put back into the patients - allowing for direct treatment of the disease, sidestepping many of the hazards linked to immune system rejections that occur if the stem cells come from another person (a donor).

Ex vivo gene therapy extracts the patient's own stem cells, corrects the faulty gene, and then places it back into the patient. Over the last four decades replacing stem cells with faulty genes has been done via donor HMC (haematopoetic stem cell) - the stem cell with correct genes is taken from one person, the donor, and inserted into the patient. For donor HNC to have a chance of working, the patient and donor must be a good "match", otherwise the patient's immune system will reject the graft. Often a match cannot be found, and even when one is, there is still a risk of rejection. With ex vivo gene therapy there is no risk of rejection, and no delay in looking for a compatible donor.

GSK will give Fondazione Telethon an upfront payment of 10 million Euros. Upon completion of specified milestones, the company will be entitled to further payments.

Dr Philippe Monteyne, Head of Development and Chief Medical Officer for GSK Rare Diseases, said:

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. 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.

Professor Luigi Naldini, Director of HSR-TIGET, said:

This collaboration is a breakthrough for gene therapy in rare diseases. 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.

Francesca Pasinelli, General Manager of Fondazione Telethon, said:

This day is one of extraordinary importance for us. 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.

Maria Grazia Roncarolo, Scientific Director of the San Raffaele Scientific Institute, said:

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

Source: GSK