Complement-ary Treatment for Alzheimer’s Disease?

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dominoesThe complement system is a complex cascade of reactions forming a central component of the innate immune system which assists in the removal of invading pathogens and cellular debris, and in the processing of immune complexes. There is substantial evidence that complement activation is associated with amyloid plaques in the brains of Alzheimer’s disease patients, although whether this is beneficial or detrimental has been unclear.

PMX-205 structureWriting in the Journal of Immunology, US and Australian scientists have now described the effect of administration of an antagonist of the receptor for the complement activation product, C5a, in animal models of Alzheimer’s disease. Oral administration of PMX205 in drinking water for 2-3 months resulted in substantial reductions in disease markers such as fibrillar amyloid deposits and activated glia in two mouse models of Alzheimer’s disease. The reduction in pathological markers correlated with improved performance in a passive avoidance task in Tg2576 mice. In 3xTg mice, PMX205 also significantly reduced hyperphosphorylated tau.

PMX205 is a cyclic hexapeptide derivative that was developed by Promics as a second generation C5a receptor antagonist for the treatment of inflammatory disorders, including inflammatory bowel disease. An earlier compound, PMX53, was found to be well tolerated in phase I clinical trials for rheumatoid arthritis and psoriasis.

The new study shows for the first time that antagonists of the C5a receptor interfere with inflammation and neurodegeneration in mouse models of Alzheimer’s disease and could, one day, lead to new treatments for human patients.


3 comments on “Complement-ary Treatment for Alzheimer’s Disease?
  1. Michael Bennett, MD says:

    Dear Sirs: Where can I purchase PMX205 for use in mouse experiments to test its effect on tumors and Alzheimer’s. Thank you for your reply.

  2. Dr.Ettore R Castiglioni says:

    How can I get some samples of this drug P M X 205 for a relavitive of mine who is suffering from Alzheimer’s Disease.

    • admin says:

      As far as I am aware, PMX-205 has not entered clinical trials. The company that developed PMX-205, Promics, was acquired by Arana, which was subsequently acquired by Cephalon. The Alzheimer’s Association provided a grant to a researcher at the University of Irvine, California in 2010 with the aim of exploring its suitability for human studies (see this link)

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