2002 French gene therapy trials

The 2002 French Gene Therapy Trials were a series of clinical trials conducted in France aimed at treating children with X-linked severe combined immunodeficiency (X-SCID), a genetic disorder that severely impairs the immune system. These trials were significant in the field of gene therapy as they demonstrated both the potential and the risks associated with this innovative treatment approach.

Background

X-linked severe combined immunodeficiency is a genetic disorder caused by mutations in the IL2RG gene, which is crucial for the development and function of immune cells. Children with X-SCID are highly susceptible to infections and typically do not survive beyond infancy without treatment. Traditional treatments include bone marrow transplants, but these are not always successful or available.

Gene therapy emerged as a promising alternative, aiming to correct the genetic defect by introducing a functional copy of the IL2RG gene into the patient's hematopoietic stem cells.

The Trials

The 2002 French trials were led by Dr. Alain Fischer and his team at the Necker Hospital in Paris. The approach involved extracting hematopoietic stem cells from the patients, using a retroviral vector to insert a functional IL2RG gene, and then reintroducing these modified cells back into the patients.

Methodology

1. Patient Selection: The trials involved young children diagnosed with X-SCID who lacked suitable bone marrow donors. 2. Gene Transfer: A retroviral vector was used to deliver the IL2RG gene into the patients' stem cells. 3. Reinfusion: The genetically modified stem cells were infused back into the patients. 4. Monitoring: Patients were closely monitored for immune function restoration and potential adverse effects.

Results

Initially, the trials were hailed as a success. The majority of the treated children showed significant improvement in immune function, allowing them to live relatively normal lives. However, within a few years, some patients developed leukemia, a serious adverse event linked to the integration of the retroviral vector near oncogenes, which activated these cancer-causing genes.

Impact and Controversy

The development of leukemia in some patients led to a temporary halt in gene therapy trials worldwide and sparked a debate about the safety of gene therapy. The trials highlighted the need for safer vector designs and better understanding of gene integration sites.

Despite the setbacks, the trials provided valuable insights that have guided subsequent advancements in gene therapy, including the development of safer vectors such as lentiviral vectors and CRISPR-Cas9 gene editing technologies.

Also see

• Gene therapy
• X-linked severe combined immunodeficiency
• Retroviral vector
• Leukemia
• CRISPR-Cas9

References

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