Gene therapy successfully treats 'Bubble Boy disease' in children
1 Nov 2017
MRC-funded scientists at the UCL Institute of Child Health have developed a successful treatment for children with ‘Bubble boy disease’, a rare immune disorder. In 2015, this work led to the launch of Orchard Therapeutics, a spin-out company which aims to further develop gene therapy to benefit patients with serious and life-threatening diseases.
Severe combined immunodeficiency (SCID) is the name given to several rare inherited diseases where children are born with defective immune systems. It is also known as the ‘Bubble boy disease’ because affected children are extremely vulnerable to infectious diseases and some of them have become famous for living in a sterile environment. In the most severe forms, children are unable to fight off even very mild infections and, without treatment, will usually die within the first year of life. Professor Bobby Gaspar at Great Ormond Street Hospital (GOSH) and the UCL Institute of Child Health has pioneered potential treatments including gene therapy for SCID, and has been supported by the MRC since 2006.
In 2015, Professor Gaspar’s work on gene therapy led to the launch of Orchard Therapeutics. In November 2016, this spin-out company received $20 million from the California Institute for Regenerative Medicine’s governing board (CIRM). The grant will fund a new, larger clinical trial for a type of SCID known as adenosine deaminase deficiency (ADA), characterised by the lack of an enzyme called adenosine deaminase. Orchard Therapeutics also announced in November 2016 that it had entered into a strategic alliance with Oxford BioMedica plc, a world-leading company in gene and cell therapy. These developments highlight the commercial potential of Professor Gaspar’s work and represent an exciting example of regenerative medicine’s ability to improve human health.
In September 2016 Professor Gaspar presented early clinical data from his ADA-SCID gene therapy trial at the European Society for Immunodeficiencies conference. 39 patients ADA-SCID have been treated at GOSH and the University of California Los Angeles. All patients were reported to have survived the treatment, and 31 out of 32 patients show signs of their immune system being reconstituted, with a favourable safety profile. Although these results are preliminary, this personalised gene therapy approach using stem cells may offer hope to patients with this life-threatening disease. Since discovering the genes responsible for SCID, researchers have been working on new and improved forms of treatment. One exciting approach is gene therapy, where the defective gene can be replaced with a functional version, thereby eliminating the cause of the disease. Gene therapy for SCID involves using the patient’s own stem cells, through a process known as an autologous stem cell transplant. Using the patient’s own stem cells provides a perfect match and eliminates the need for a donor search, along with the associated risk of complications such as transplant rejection. The stem cells are taken from the patient through a bone marrow extract and then genetically corrected outside of the body by replacing the missing or faulty gene. These corrected cells are then transplanted back into the body, through an intravenous infusion. Sometimes the patient is given mild chemotherapy before the transplant; this is done to eliminate any existing stem cells that carry the genetic defect so that the new engineered cells can repopulate the bone marrow more effectively after the transplant.