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1403 The EIF4 translational inhibitor pateamine a improves immunological and neurological functions in BXSB.yaa lupus mice
  1. Gonzalo Gómez-Hernández1,
  2. Nieves Varela1,
  3. Harini Bagavant2,
  4. Guillermo Barturen1,
  5. María Morell1 and
  6. Marta E Alarcón-Riquelme1
  1. 1Genyo, Granada, Spain
  2. 2OMRF, Oklahoma City, USA


Background Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance and activation of the immune response. Clinical manifestations are heterogeneous and several organs can be affected including skin, joints, central nervous system and kidney. Traditional treatments include the use of hydroxychloroquine, glucocorticosteroids, immunosuppressive and more recently, biological drugs such as belimumab or rituximab. In the last decade new alternatives have been proposed based on targeting interferon and cytokines. Mouse models have been extremely helpful to test the efficacy of new SLE therapies. In this work we analyze the therapeutic potential of a natural compound, Patemina A (PatA) to treat SLE. Pat A is an inhibitor of the translation initiation process with immunosuppressive properties that has been tested successfully in cancer mouse models.

Methods To test Pat A efficiency in SLE we used the BXSB.Yaa lupus model. Animals were treated for 8 weeks starting at the initial stages of disease (12 weeks). Sera was collected every three weeks and disease signs were followed. At the final point we performed serological analyses (cytokines and autoantibodies), flow cytometry on spleen to evaluate different cell populations, kidney histological and functional assays and behavioral tests to evaluate neuropsychiatric changes.

Results Our data shows that Pat A treatment increases the survival rate and is able to reduce circulating levels of proinflammatory cytokines and autoantibodies. We also observed improvement of cognitive functions (learning/memory, and depression behavioral tests) together with a reduction of proinflammatory cytokines locally in the hippocampus.

Conclusion These data suggests that translation inhibition improves lupus disease signs at the immunological and neurological levels opening a new line of research based on translation inhibition to treat lupus and possibly other autoimmune diseases with an inflammatory component, and may be a complement for present day treatments.

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