Team 6- CNS Gene Transfer & Biotherapy of Motor Neuron Diseases

Team leader- Martine Barkats

The main goal of our team is to identify efficient strategies to target the central nervous system (CNS) and to develop novel therapies for motor neuron disorders. In particular, we focus on Spinal Muscular Atrophy (SMA) and Amyotrophic Lateral Sclerosis (ALS), two yet incurable diseases.

Our studies opened new perspectives and applications for the treatment of CNS diseases and other diseases, based on the use of Adeno-Associated Virus (AAV) vectors. Indeed, our team discovered the unique therapeutic potential of self-complementary AAV serotype 9 vectors (AAV9) in the setting of global gene transfer to the CNS following systemic (intravenous and intramuscular) delivery (Barkats, patent PCT/EP2008/063297, 2007; Duque et al., 2009; Benkhelifa-Ziyyat et al., 2013). We also recently demonstrated that AAV serotype 10 (AAV10), delivered systemically, outperforms AAV9 for gene transfer to CNS and peripheral organs (Tanguy et al., 2015).

Taking advantage of AAV vectors potential to target CNS, we developed an efficient gene therapy for SMA able to extend survival and improve the phenotype of a severe SMA mouse model (Dominguez et al., 2011). Interestingly, a phase I/II clinical trial, using a similar approach, is currently undergoing in USA for SMA type 1 patients (NCT02122952).
More recently, we have developed an innovative technique for the treatment of ALS linked to Superoxide dismutase 1 (SOD1) mutations. Using an exon-skipping approach and AAV vectors, we induced a strong, body-wide reduction of mutant hSOD1 in the well-characterized SOD1G93A mouse model (Biferi et al., 2017). This therapeutic strategy has been awarded by the “THE $1M AVI KREMER ALS TREATMENT PRIZE4LIFE”.




Our projects are aimed to:

  • Optimize the gene therapies for SMA and ALS
  • Develop new therapeutic approaches for motor neuron disorders
  • Understand the pathophysiology of these complex diseases


Team members

Martine Barkats (Team leader, DR2, HDR, INSERM)
Maria Grazia Biferi (Principal investigator, CR, AIM)
Thibaut Marais (Engineer – AIM)
Stéphanie Astord (Engineer – AIM)
Mathilde Cohen-Tannoudji (Engineer – AIM)
Aurore Besse (Engineer and PhD student – UPEC)
Jordan Mecca (PhD student – Sorbonne University)
Corinne Bos (PhD student- Sorbonne University)

Postdoctoral researchers to be recruited



Martine Barkats:
Maria Grazia Biferi: