Innovative Therapy divisions (Service des Thérapies Innovantes – STI), directed by Pr Philippe Leboulch, is responsible for the development of new molecular and cellular approaches to the treatment of innate or acquired genetic diseases.

Our research is based around two approaches.

The first concerns the cell therapy  (expansion ex vivo of cell populations) and the gene therapy (gene transfer and correction). We participated in the first successful clinical trial of gene therapy for b-thalassemia.

The second approach involves studies of the molecular mechanisms controlling the proliferation and differentiation of somatic cells, physiopathogenic processes targeted by many cell therapy strategies. Our work involves the characterization of new connections between transcription factors, cell signaling and knowledge of the control of the balance between proliferation and differentiation in normal and pathological (cancer) cells.

iMETI/STI is composed of two laboratories, as indicated in the organigram. Specific scientific research projects were as follows:

1. To pursue basic research and clinical development towards a safe and effective gene therapy approach for the beta‐hemoglobinopathies (beta‐thalassemia and sickle cell disease), as a prototypical model of lentiviral hematopoietic gene therapy. In particular, P. Leboulch is the scientific director of the human clinical trial entitled "A Phase I/II Open Label Study With Anticipated Clinical Benefit Evaluating Genetic Therapy of the βHemoglobinopathies (Sickle Cell Anemia and βThalassemia Major) by Transplantation of Autologous CD34+ Stem Cells Modified ExVivo with a Lentiviral βAT87QGlobin (LentiGlobinTM) Vector". This trial is ‐together with that for adrenoleukodystrophy ‐ the first worldwide clinical trial having received regulatory approval for the use of a lentiviral vector for the ex vivo gene therapy of inherited genetic disorders.

2. To contribute to other areas of hematopoietic gene therapy and cancer.

3. To investigate novel approaches for the controlled expansion of hematopoietic stem cells (HSCs).

4. To contribute to the elucidation of the molecular mechanisms that control the balance between cell proliferation and differentiation or cell quiescence and differentiation in normal and pathological (cancer) hematopoietic cells.

5. To set up a platform for autologous hematopoietic transplantation with gene transfer in non‐human primates.

6. To set up a platform for high‐throughput screening of small molecules capable of expanding HSC populations.

7. To set up an iPS platform in non‐human primates.

​​​​​FIRST SUCCESS IN A CLINICAL TRIAL OF GENE THERAPY FOR BETA-THALASSEMIA

The STI also studies the molecular mechanisms controlling the proliferation and differentiation of somatic cells, the balance between these two processes being at the heart of a large number of physiopathogenic processes and many cell therapy strategies. We were involved in the characterization of new connections between transcription factors, cell signaling and knowledge about control of the proliferation/differentiation balance (e.g. GATA-FOG-pRb and PPARgamma-STAT5; PLoS Biology 2009; JCI, 2008).