Rare Diseases Symptoms Automatic Extraction

Cell- and protein-based therapy approaches for epidermolysis bullosa.

[dystrophic epidermolysis bullosa]

Dystrophic epidermolysis bullosa (DEB) is a clinically heterogeneous heritable skin fragility disorder characterized by mechanically induced mucocutaneous blistering. On the molecular level DEB is caused by mutations leading to deficiency in collagen VII (CVII), a large extracellular protein building anchoring fibrils that attach the epidermis to the dermis. Severely affected patients suffer from wounds, which heal with excessive scarring causing mutilating deformities of hands and feet. The patients are also predisposed to development of aggressive squamous cell carcinomas at sites of chronic wounds. Currently no available therapies exist for this extremely disabling and stigmatizing disorder. We are developing and evaluating cell- and protein-based therapies for the management of DEB. Dermal fibroblasts are easy to propagate in vitro, they produce CVII, and they have immunomodulating capacities, which makes it possible to use allogeneic fibroblasts for therapy without risking major adverse effects from the host's immune system. Hence, fibroblasts, and fibroblast-like cells such as mesenchymal stromal cells, are prime candidates for cell-based DEB therapies. An alternative for management of disorders caused by defects in proteins with relatively low turnover rate is to introduce the protein de novo to the tissue by direct application of the protein. CVII is long-lived and expressed in moderate amounts in the skin; this makes injection of collagen VII protein a realistic approach for the treatment of DEB. Here we present methods and protocols that we are using for fibroblast- and recombinant CVII-based therapies of DEB in our model of this disease, the CVII hypomorphic mouse. These protocols are directed towards management of DEB but they can be easily adapted for the treatment of other skin fragility disorders.

Diseases presenting "defects in proteins with relatively low turnover rate is to introduce the protein de novo to the tissue by direct application of the protein" symptom

  • dystrophic epidermolysis bullosa

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