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Projects. Life and Matter Sciences

Activation of innate immunity pathways in dysferlin-deficient cells: new therapeutic targets

Lead Researcher: Noemí de Luna Salvà
Research Centre: Laboratorio de Enfermedades Neuromusculares.
Hospital de la Santa Creu y Sant Pau. Barcelona. CIBER (Centro de Investigación Biomédica en Red).


Noemí de Luna SalvàThe overall objective of this project is to study the signalling pathways involved in the muscle inflammation observed in dysferlinopathy patients to discover potential therapeutic targets to improve the muscle phenotype.

The specific objectives are:

  1. To identify alarmins secretion by dysferlin-deficient skeletal muscle and study cell signalling through Toll-like receptors (TLR).
  2. A therapeutic approach will be assessed using different drugs:
    • a)  Blockade of TLRs signalling pathways (TLR antagonists, Atorvastatin) to prevent the release of inflammatory cytokines.
    • b) Proteasome inhibition (Oprozomib- Marizomib) to block premature degradation of dysferlin with missense mutations which could be partially functional.
    • c) To study the effect of combining vitamin D3 with the different drugs tested in a) and b).
  3. Finally, if the treatments tested "in vitro" show positive results, we will perform "in vivo" experiments in dysferlin-deficient mouse models.

Methods: Skeletal muscle primary cultures from wild type and dysferlin-deficient mice and human muscle biopsies, dysferlin gene edition using CRISPR/cas9 technology to reproduce mutations of patients with dysferlinopathy, immunohistochemistry, Western Blot, real-time PCR, ELISA.

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