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Rare Diseases

Rare diseases — defined by a prevalence below one person in 2,000 — represent, by their sheer number, a considerable health challenge: several thousand are known, most of them still without curative treatment. Often genetic in origin, they call for a detailed understanding of their molecular causes and the development of specific treatments, including orphan drugs.

The work to which Inovarion has contributed in this field clusters around three families of diseases. Cystic fibrosis first, with the study of modifier genes that influence disease severity[8], a genome-wide association study of susceptibility to Pseudomonas aeruginosa infection[4], and the analysis of seasonal influence on respiratory infections[5] — work at the crossroads of genetics and epidemiology. The modifier genes identified, such as SLC26A9, and CFTR-protein modulators open avenues to explain and, ultimately, to attenuate the clinical heterogeneity of the disease.

Rare bleeding disorders next: von Willebrand disease (a humanised mouse model[1], a nanobody directed against von Willebrand factor[6]) and haemophilia A and B (antithrombin targeting, the equivalence of non-factor therapies to factor VIII[3]). The humanised mouse model of von Willebrand disease is, in this respect, a valuable platform for testing new therapeutic approaches.

Duchenne muscular dystrophy finally: the role of the CD38/NAD+ axis in the dystrophic phenotype[9], the inflammatory consequences on the myocardium of dystrophin-replacement therapies[2], and the regulation of muscle calcium homeostasis (NR1D1/myoregulin)[10]. AAV-vectorised micro-dystrophin gene therapy is evaluated here, including its long-term effects on the heart.

Beyond these three families, rare diseases form a cross-cutting dimension of Inovarion’s achievements: other work concerns, for example, achondroplasia, Bernard-Soulier syndrome or Erdheim-Chester disease.

This research mobilises genome-wide association studies and polygenic risk scores, Mendelian randomisation, humanised mouse models and disease models (mdx, double knock-out), nanobodies and AAV-vector gene therapy, as well as transcriptomics. This work has appeared in Blood, Haematologica, EMBO Molecular Medicine, European Respiratory Journal and JACC: Basic to Translational Science.

Because they often demand dedicated models and a deep genetic understanding, rare diseases call on the full range of Inovarion’s expertise. The laboratory thus brings together, for its partners, genetics, animal models, antibodies and gene therapy.

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Representative publications

  1. McCluskey et al. A fully humanized von Willebrand disease type 1 mouse model as unique platform to investigate novel therapeutic options. Haematologica, 2025. Record → · PubMed
  2. Forand et al. Long-Term Dystrophin Replacement Therapy in Duchenne Muscular Dystrophy Causes Cardiac Inflammation. JACC Basic Transl Sci, 2025. Record → · PubMed
  3. Sefiane et al. Consistent clinical factor VIII equivalency is unlikely for non-factor therapies in hemophilic mice. Haematologica, 2025. Record → · PubMed
  4. Lin et al. Genome-wide association study of susceptibility to Pseudomonas aeruginosa infection in cystic fibrosis. Eur Respir J, 2024. Record → · PubMed
  5. Mésinèle et al. Seasonal and climatic influence on respiratory infections in children with cystic fibrosis. Scientific Reports, 2024. Record → · PubMed
  6. Kizlik-Masson et al. A nanobody against the VWF A3 domain detects ADAMTS13-induced proteolysis in congenital and acquired VWD. Blood, 2023. Record → · PubMed
  7. Mésinèle et al. Airway infections as a risk factor for Pseudomonas aeruginosa acquisition and chronic colonisation in children with cystic fibrosis. J Cyst Fibros, 2023. Record → · PubMed
  8. Mésinèle et al. Modifier Factors of Cystic Fibrosis Phenotypes: A Focus on Modifier Genes. Int J Mol Sci, 2022. Record → · PubMed
  9. Zélicourt et al. CD38-NADase is a new major contributor to Duchenne muscular dystrophic phenotype. EMBO Mol Med, 2022. Record → · PubMed
  10. Boulinguiez et al. NR1D1 controls skeletal muscle calcium homeostasis through myoregulin repression. JCI Insight, 2022. Record → · PubMed