DISCOVERY of a DNA vaccine that systemically allays chronic inflammation has led to the validation of its preventative and therapeutic impact on mouse models with osteoporosis.
The vaccine, a plasmid encoding gene for p62-SQSTM1 developed by the international CureLab consortium, has previously shown great potential for treating dogs with spontaneous mammary carcinomas, and demonstrated anti-cancer effects in melanoma, sarcoma, lung cancer, and mammary carcinomas in mouse models.
P62 is an intracellular protein that is composed of at least nine domains, and it plays a crucial role in autophagy. Cancer cells use excessive amounts of autophagy to protect themselves from radiation and chemotherapy, and cannot form a tumour if p62 is absent. This means that the application of the p62 DNA vaccine would not result in selection of p62-negative cells, which would avoid the effects of the vaccination. The vaccine is not only confined to the treatment of cancer cells; it can also be used to treat osteoporosis. P62 also functions as a cell’s signalling hub, controlling the expression of multiple genes; this means that the vaccine could be administered as an intramuscular injection, serving as a gene therapy which forces cells to express and release certain proteins.
Delighted with the potential of this product, the consortium have tested this idea in mice that have undergone ovariectomy, a procedure that causes the depletion of oestrogen, thus facilitating and mimicking the ageing process. The team observed significant down-regulation of master inflammatory cytokines by bone marrow stromal cells, implying that the p62 DNA vaccine could have a positive effect on reducing or completely eliminating known inflammatory diseases including osteoporosis. The intramuscular supply of p62 DNA exerted an anti-osteoporotic action in mouse models with inflammatory bone loss, potentially paving the way for its application as a new therapy for treating inflammatory-related bone loss.
“I do not believe in panaceas, still chronic inflammation manifests itself in almost every disease associated with age,” said author Prof Franco Venanzi, School of Biosciences and Biotechnology, University of Camerino, Camerino, Italy. “The more we test our p62 vaccine and its derivatives on different models of inflammatory diseases, the more excited and hopeful we are.”