Laboratoire Biothérapies des Maladies Neuromusculaires (UVSQ)

The laboratory “biothérapies of neuromuscular diseases” is part of a mixed research unit (U1179-UVSQ-Inserm) based at the Faculty of Health Sciences of the University of Versailles Saint Quentin en Yvelines, France. The U1179 unit has nearly 1000 m2 in the Faculty of Health Sciences building and access to the all technical platforms of the site, including platforms for imaging, cytometry, genomics, mass spectrometry, histology, animal testing and a level 3 confined laboratory.

The group has a renowned leadership in the field of gene therapy and antisense technology to correct the deleterious effects of mutations in various genetic diseases, and in particular for the treatment of neuromuscular diseases such as Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA). The UVSQ partner has a long-standing expertise in the pre-clinical evaluation of antisense strategies, using both naked antisense oligonucleotides and vectorised approach (AAV-U7), which will be used in this research project. In particular, the group has been collaborating for many years with the SME Synthena (also in BIND) and has demonstrated the unique ability of tricyclo-DNA to cross the blood brain barrier after systemic delivery.

Moreover, the group has been collaborating with the group of Cyrille Vaillend at Paris-Saclay Institute of Neuroscience in Orsay (partner “CNRS”) and has generated very exciting preliminary data for this research project, indicating that at least some of the CNS manifestations of dystrophin deficiency in the brain can be rescued postnatally. This successful collaboration has already led to several joint publications and the ongoing co-direction of a PhD student.

Partner UVSQ leads the WP4 – Impact of brain dystrophins restoration on dystrophic mice phenotype. The aim of this WP is to assess the impact that postnatal restoration of dystrophin expression has on neuropsychological / behavioural features in the different mdx mouse models using antisense exon skipping technologies. Various tools, all available in the consortium, will be investigated including synthetic antisense oligonucleotides (PMO, 2’MOE, tcDNA, PPMO) and vectorized systems (AAV-U7snRNA) as well as direct AAV gene replacement for Dp71.

Team

Aurélie Goyenvalle

Dr Aurélie Goyenvalle

Position in Organisation
Head of laboratory– permanent scientist (INSERM)

Profile and role in the project
Dr. Aurélie Goyenvalle has pioneered the antisense mediated exon skipping for DMD, using viral vectors as well as antisense oligonucleotides (AONs). Since 2012 her group has been developing novel RNA based strategies for the treatment of neuromuscular diseases at the University of Versailles Saint Quentin en Yvelines (UVSQ). She has notably demonstrated the therapeutic potential of a novel class of AONs made of tricyclo-DNA (tcDNA), which displays unique pharmacological properties and unprecedented uptake in many tissues after systemic administration.

Dr Goyenvalle is a renowned expert in antisense approaches and AON drug development, and a member of the COST Actions BM1207 “Networking towards clinical implementation of antisense-mediated exon skipping for rare diseases” and CA17103 “Delivery of Antisense RNA Therapeutics”. Dr Goyenvalle will be the lead contact for UVSQ and coordinate the WP4 – Impact of brain dystrophins restoration on dystrophic mice phenotype.

Ophélie Vacca

Position in Organisation
Postdoctoral scientist

Profile and role in the project
Ophélie Vacca has a PhD in gene therapy and dystrophies. Within the BIND project, she will develop different antisense tools (antisense oligonucleotides and AAV vectors) targeting different DMD exons to restore the expression of brain dystrophin isoforms and assess the impact that postnatal restoration of dystrophin expression has on neuropsychological /behavioural features in DMD mouse models. She is supervised by dr Goyenvalle and will organize the experimental design and carry out the experiments. Together they will analyse the data generated and coordinate with the relevant persons within and outside the project to insure a proper work flow.

Amel Saoudi

Ms Amel Saoudi

Position in Organisation
PhD student

Profile and role in the project
Amel Saoudi is a young and motivated PhD student who has joined the group in October 2019 under the co-supervison of Dr Goyenvalle at UVSQ and Dr Vaillend at CNRS. Amel will be involved in the characterisation of neuropsychological / behavioural features in the mdx52 mouse model (WP3) and in the assessment of exon 51 skipping in the brain of this model (WP4), in particular using tcDNA-AON. Amel is trained on behabioral assessment as well as injection techniques for all the in vivo work and all the molecular biology techniques required (exon skipping analysis, dystrophin WB, etc.).

Arnaud Delimoges

Mr Arnaud Delimoges

Position in Organisation
Director of the Engineering division of international projects

Profile and role in the project
Arnaud Delimoges, with his team from the Engineering division of international projects at UVSQ, assists professor-researchers and researchers in their applications for international research programmes, including Horizon 2020, and monitors the implementation of funded projects. As part of the BIND project, the team will be in charge of monitoring the project for all the non scientific parts, in conjunction with the services of the UVSQ and the project management team.