6- Biotherapies for motor neuron disorders (ALS & SMA) Group


Group leader: Piera Smeriglio

The main goal of our team is to develop new therapies for motor neuron disorders (MND). Our work is focused on spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS).

The use of viral vectors derived from adeno associated virus (AAV) opened novel perspectives and applications for the treatment of MNDs. 

In 2007, M. Barkats demonstrated the high potential of self-complementary AAV serotype 9 (AAV9) to efficiently transduce the central nervous system (CNS) following a systemic injection (Barkats, Patent PCT/EP2008/063297, 2007 and Martine Barkats and AAV9-SMN: from discovery to treatment). Remarkably, the first gene therapy based on this approach – Zolgensma®, – has been recently approved by the Food and Drug Administration (FDA) for the treatment of infantile forms of SMA. This represents a major breakthrough in the field of gene therapy for rare diseases.



  • We are currently optimizing the AAV-mediated gene replacement approach for SMA. Our objective is to develop specific vectors targeting multiple organs affected in the disease. This will likely reduce the potential side-effects of the current therapy on the long term. We are also investigating epigenetic regulation in SMA and motor neuron degeneration. The study of epigenetic hallmarks will provide a comprehensive understanding of the disease and in particular of its different forms. Furthermore, this work will contribute to the identification of novel pathways implicated in the pathophysiology of SMA.
    The objective of these projects on the long term is to identify novel therapeutic targets, specific to each SMA patient and to design future personalized medicine approaches. 
  • We are also taking advantage of the therapeutic potential of AAV vectors to find treatments for ALS. In 2017, we developed a therapeutic strategy for ALS caused by mutations in the superoxide dismutase 1 (SOD1) gene. Using an exon-skipping approach through AAV, we induced global decrease in the human mutant SOD1 in the SOD1G93A mouse model (Biferi et al., 2017). This work received the Prize4Life award “THE $1M AVI KREMER ALS TREATMENT PRIZE4LIFE”. We are currently furthering the pre-clinical development of this approach in collaboration with Généthon.
  • A big part of our research effort focuses on the development of a therapeutic strategy for ALS and fronto-temporal dementia (FTD) caused by mutations in C9ORF72 gene. This is the most common form of ALS (40% of familial forms and 7% of sporadic cases). The mutation results in a gain-of-function and a loss of C9ORF72 protein expression (Reviewed by Cappella et al., IJMS 2019). Our strategy aims to simultaneously target all the pathological mechanisms, using AAV vectors. We are also generating novel experimental models to better understand the disease.



Composition and expertise of the group

BOND team members Expertises
Permanent positions Piera Smeriglio (Team leader)
Martine Barkats (Research director, INSERM)
Thibaut Marais (Engineer, AIM)
Stéphanie Astord (Engineer, AIM)
Mathilde Cohen-Tannoudji (Engineer, AIM)
• Gene delivery in the central nervous system and skeletal muscle
• Fundamental and translational research for motoneuron diseases (ALS and SMA)
•  Experimental models
•  AAV design and production



Non permanent positions


Marisa Cappella (Post-doc, INSERM)
Sahar Elouej (Post-doc, INSERM)
•  Clinical neurology of ALS and SMA
•  Epigenetics and Stem cells
•  Genome-editing and RNA biology
•  Bioinformatics
Georges Arielle Peche (Research assistant, INSERM)
Sonia Pezet (Engineer, INSERM)
Marine Delamare (Engineer, INSERM)
Mohamed Zerara (Engineer, INSERM)
• Pathophysiology of neuromuscular diseases
• Experimental models



Piera Smeriglio : p.smeriglio@institut-myologie.org


Last publications



Gene Therapy for ALS-A Perspective.(2019) Cappella M, Ciotti C, Cohen-Tannoudji M, Biferi MG. Int J Mol Sci. 2019 Sep 6;20(18). pii: E4388. doi: 10.3390/ijms20184388. Review. PMID: 31500113



  • Biferi M.G., Cappella M., Barkats M. Antisense sequences for treating amyotrophic lateral sclerosis (AIM). April 2020. EP20169064.1
  • Barkats M., Biferi M.G., Voit T. Treatment of Amyotrophic Lateral Sclerosis. (AIM, CNRS, INSERM, UPMC). July 2014. WO2016016449 A1