Gene Therapy of Haematopoietic Stem Cells in Patients with X-linked Severe Combined Immunodeficiency

In this clinical research project, haematopoietic stem cells are isolated and purified from the blood of children who have X-linked Severe Combined Immunodeficiency, arising from a point mutation in the Gamma-C gene. The isolated haematopoietic stem cells will be cultured and repeatedly infected using an integrating retrovirus in order to genetically modify them with the normal version of the Gamma-C gene, before they are re-introduced into the children.

As the final product is intended for human application, the research establishment requires a licence from the Human Tissue Authority (HTA). The research initially involves the laboratory use of genetic modification which requires a notification to the Health and Safety Executive (HSE). The project also initially involves preclinical research in mice. These experiments should take place under conditions of Good Laboratory Practice (GLP; See Glossary) but only after consultation with the Medicines and Healthcare products Regulatory Agency (MHRA) and with the approval of the Home Office Animal Licensing Inspectorate.

The cells to be introduced into patients are cultured and modified under Good Manufacturing Practice (GMP; See Glossary). Because the clinical study involves the use of an Investigational Medicinal Product (IMP; See Glossary), the approval of the MHRA Clinical Trials Unit is required. The additional use of genetically modified cells in patients requires a further notification to the HSE. In addition, the clinical trial requires a Favourable Opinion from the Gene Therapy Advisory Committee (GTAC) because it involves the use of a gene therapy medicinal product. Approval of the local National Health Service Research and Development (NHS R&D) office is also required.

After sufficient quality, safety and efficacy data have been obtained in clinical trials, an application can be made to the European Medicines Agency (EMEA) to obtain Marketing Authorisation to use the therapy as a standard treatment.

To view the Regulatory Route Map for this project, click on the route code M-90590. Alternatively, to see the Project View for this Regulatory Route, click on P-90590.