Elvire GOUZE

Development of biotherapies for skeletal dysplasia

Main interests

  • development of innovative biotherapies for skeletal dysplasia
  • unmet medical need
  • interests in rare genetic bone diseases with main focus on achondroplasia and type II collagenopathies
  • choice of the most appropriate strategy depending on the disease (protein, gene or stem cell therapy)

Scientific Questions

Our goals are to develop innovative therapies for skeletal dysplasia.

Skeletal dysplasia represent a heterogeneous group of rare disorders comprising a large number of pathologies associated with orthopedic complications, dwarfism or gigantism. More than 350 disorders have been identified. They are caused by genetic mutations that modify or inhibit the development of cartilages or bones. These mutations can for example affect matrix proteins, transcription factors, signal transducers, or intracellular binding proteins. Diagnosis is mainly based on clinical and radiographic observations, and confirmed by molecular testing, allowing also for the classification of the different types of known skeletal dysplasia.

Our team is currently focusing on achondroplasia and SEDc (spondyloepiphyseal dysplasia congenita), a type II collagenopathy.

Our Strategy

To develop these innovative therapies, we have a 4-steps strategy. Depending on the disease, we develop recombinant protein approaches a well as gene and cell therapies.

1. The therapeutic approach is first evaluated in vitro. This step also allows us to decipher the mechanism of action.

2. The experimental proof-of-concept is demonstrated using mouse models recapitulating the human disease. Potential side effects are carefully evaluated at this stage. This step allows to perform the translational development of the therapeutic strategy.

3. Treatment effects on whole body are studied in detail. These fundamental aspects are key in understanding the non-osseous symptoms of these pathologies. These aspects are often neglected and not well known.

4. Data are then used to complete the preclinical development and conduct clinical trials. This step is done in close relationship with the patient associations.

Research Aims

We are first focusing on the preclinical development of a biotherapy for achondroplasia in close collaboration with Therachon (www.therachon.com). We pay a particular emphasis on understanding treatment effects on the metabolic tissues. This aspect of the project requires first the fundamental understanding of the role of the FGFR3 mutation on the metabolic deregulations observed in achondroplasia patients. We are developing a recombinant protein approach using Fgfr3ach/+ mice.

Our second project aims at developing innovative therapies for type II collagenopathies, a group of skeletal dysplasia that result from heterozygous mutations in the type II collagen gene (COL2A1). This project focuses on SEDc, the most common non-lethal type II collagenopathy. Several mutations in the COL2A1 gene have been identified in SEDc patients and are directly responsible for the clinical features. We are developing an ex vivo gene therapy approach using SEDc mice.


BERTOLA Adeline - +33 489150851


Recent publications

  1. Gonçalves, D, Rignol, G, Dellugat, P, Hartmann, G, Sarrazy Garcia, S, Stavenhagen, J et al.. In vitro and in vivo characterization of Recifercept, a soluble fibroblast growth factor receptor 3, as treatment for achondroplasia. PLoS One. 2020;15 (12):e0244368. doi: 10.1371/journal.pone.0244368. PubMed PMID:33370388 PubMed Central PMC7769458.
  2. Saint-Laurent, C, Garde-Etayo, L, Gouze, E. Obesity in achondroplasia patients: from evidence to medical monitoring. Orphanet J Rare Dis. 2019;14 (1):253. doi: 10.1186/s13023-019-1247-6. PubMed PMID:31727132 PubMed Central PMC6854721.
  3. Saint-Laurent, C, Garcia, S, Sarrazy, V, Dumas, K, Authier, F, Sore, S et al.. Early postnatal soluble FGFR3 therapy prevents the atypical development of obesity in achondroplasia. PLoS One. 2018;13 (4):e0195876. doi: 10.1371/journal.pone.0195876. PubMed PMID:29652901 PubMed Central PMC5898762.
  4. Unger, S, Bonafé, L, Gouze, E. Current Care and Investigational Therapies in Achondroplasia. Curr Osteoporos Rep. 2017;15 (2):53-60. doi: 10.1007/s11914-017-0347-2. PubMed PMID:28224446 PubMed Central PMC5435778.
  5. Garcia, S, Dirat, B, Tognacci, T, Rochet, N, Mouska, X, Bonnafous, S et al.. Postnatal soluble FGFR3 therapy rescues achondroplasia symptoms and restores bone growth in mice. Sci Transl Med. 2013;5 (203):203ra124. doi: 10.1126/scitranslmed.3006247. PubMed PMID:24048522 .
  6. Allen, KD, Adams, SB Jr, Mata, BA, Shamji, MF, Gouze, E, Jing, L et al.. Gait and behavior in an IL1β-mediated model of rat knee arthritis and effects of an IL1 antagonist. J Orthop Res. 2011;29 (5):694-703. doi: 10.1002/jor.21309. PubMed PMID:21437948 PubMed Central PMC3100769.
  7. Watson, RS, Gouze, E, Levings, PP, Bush, ML, Kay, JD, Jorgensen, MS et al.. Gene delivery of TGF-β1 induces arthrofibrosis and chondrometaplasia of synovium in vivo. Lab Invest. 2010;90 (11):1615-27. doi: 10.1038/labinvest.2010.145. PubMed PMID:20697373 PubMed Central PMC3724510.
  8. Kay, JD, Gouze, E, Oligino, TJ, Gouze, JN, Watson, RS, Levings, PP et al.. Intra-articular gene delivery and expression of interleukin-1Ra mediated by self-complementary adeno-associated virus. J Gene Med. 2009;11 (7):605-14. doi: 10.1002/jgm.1334. PubMed PMID:19384892 PubMed Central PMC2876984.
  9. Ghivizzani, SC, Gouze, E, Gouze, JN, Kay, JD, Bush, ML, Watson, RS et al.. Perspectives on the use of gene therapy for chronic joint diseases. Curr Gene Ther. 2008;8 (4):273-86. doi: 10.2174/156652308785160638. PubMed PMID:18691023 PubMed Central PMC4350777.
  10. Evans, CH, Palmer, GD, Pascher, A, Porter, R, Kwong, FN, Gouze, E et al.. Facilitated endogenous repair: making tissue engineering simple, practical, and economical. Tissue Eng. 2007;13 (8):1987-93. doi: 10.1089/ten.2006.0302. PubMed PMID:17518747 .
  11. Gouze, E, Gouze, JN, Palmer, GD, Pilapil, C, Evans, CH, Ghivizzani, SC et al.. Transgene persistence and cell turnover in the diarthrodial joint: implications for gene therapy of chronic joint diseases. Mol Ther. 2007;15 (6):1114-20. doi: 10.1038/sj.mt.6300151. PubMed PMID:17440444 .
  12. Gouze, JN, Evans, CH, Ghivizzani, SC, Gouze, E. [Gene therapy for osteoarticular disorders]. Med Sci (Paris). 2007;23 (3):303-9. doi: 10.1051/medsci/2007233303. PubMed PMID:17349293 .
  13. Gouze, JN, Gouze, E, Popp, MP, Bush, ML, Dacanay, EA, Kay, JD et al.. Exogenous glucosamine globally protects chondrocytes from the arthritogenic effects of IL-1beta. Arthritis Res Ther. 2006;8 (6):R173. doi: 10.1186/ar2082. PubMed PMID:17109745 PubMed Central PMC1794517.
  14. Evans, CH, Ghivizzani, SC, Gouze, E, Rediske, JJ, Schwarz, EM, Robbins, PD et al.. The 3rd International Meeting on Gene Therapy in Rheumatology and Orthopaedics. Arthritis Res Ther. 2005;7 (6):273-8. doi: 10.1186/ar1853. PubMed PMID:16277703 PubMed Central PMC1297596.
  15. Palmer, GD, Steinert, A, Pascher, A, Gouze, E, Gouze, JN, Betz, O et al.. Gene-induced chondrogenesis of primary mesenchymal stem cells in vitro. Mol Ther. 2005;12 (2):219-28. doi: 10.1016/j.ymthe.2005.03.024. PubMed PMID:16043093 .
  16. Pascher, A, Steinert, AF, Palmer, GD, Betz, O, Gouze, JN, Gouze, E et al.. Enhanced repair of the anterior cruciate ligament by in situ gene transfer: evaluation in an in vitro model. Mol Ther. 2004;10 (2):327-36. doi: 10.1016/j.ymthe.2004.03.012. PubMed PMID:15294179 .
  17. Gouze, JN, Stoddart, MJ, Gouze, E, Palmer, GD, Ghivizzani, SC, Grodzinsky, AJ et al.. In vitro gene transfer to chondrocytes and synovial fibroblasts by adenoviral vectors. Methods Mol Med. 2004;100 :147-64. doi: 10.1385/1-59259-810-2:147. PubMed PMID:15280594 .
  18. Gouze, JN, Gouze, E, Palmer, GD, Liew, VS, Pascher, A, Betz, OB et al.. A comparative study of the inhibitory effects of interleukin-1 receptor antagonist following administration as a recombinant protein or by gene transfer. Arthritis Res Ther. 2003;5 (5):R301-9. doi: 10.1186/ar795. PubMed PMID:12932294 PubMed Central PMC193732.
  19. Gouze, E, Pawliuk, R, Gouze, JN, Pilapil, C, Fleet, C, Palmer, GD et al.. Lentiviral-mediated gene delivery to synovium: potent intra-articular expression with amplification by inflammation. Mol Ther. 2003;7 (4):460-6. doi: 10.1016/s1525-0016(03)00024-8. PubMed PMID:12727108 .
  20. Palmer, G, Pascher, A, Gouze, E, Gouze, JN, Betz, O, Spector, M et al.. Development of gene-based therapies for cartilage repair. Crit Rev Eukaryot Gene Expr. 2002;12 (4):259-73. doi: 10.1615/critreveukaryotgeneexpr.v12.i4.20. PubMed PMID:12641395 .
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2015 - 35 Millions USD raised by Therachon to fight Dwarfism

2006 - Initiative Post-Doc, Ministère délégué à l’Enseignement Supérieur et à la Recherche

2003 - Poster of Distinction Award, Brigham and Women’s Hospital Research Council, 2nd place, Harvard Medical School

2002 - C. Gordon Van Arman Award, Inflammation Research Association, 1st place

1998 - Michel and Lydie Wittner Foundation Research Award, Fondation de France, College of Medicine, University of Henri Poincaré-Nancy I, 1st place

20M€ for InnoSkel, a new start-up launched by Elvire Gouze at iBV

The 'institut de Biologie Valrose' (iBV) is very proud to announce the launch of InnoSkel, a new start-up led by ...
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UCA Annual Award Ceremony 2019: 4 iBV members recognized this year !

It is now a tradition and highlight at the Université Cote d’Azur (UCA): the Annual Award Ceremony to recognize awardees ...
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Pfizer acquires TherAchon, the iBV hosted biotech company involved in curing skeletal dysplasia

The ‘institut de Biologie Valrose’ (iBV) congratulates Elvire Gouze, Group Leader at iBV (http://ibv.unice.fr/research-team/gouze/), for her visionary and successful project ...
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iBV - Institut de Biologie Valrose

"Sciences Naturelles"

Université Nice Sophia Antipolis
Faculté des Sciences
Parc Valrose
06108 Nice cedex 2