Methods of Treating or Preventing Autoimmune Conditions

Description: The innate immune system is the first line of host defense against pathogens. Innate immune cells, such as dendritic cells and macrophages, are first activated and subsequently trigger the generation of optimal adaptive immune responses. Although these cells lack the highly specific antigen receptors of B cells and T cells, they can detect pathogens by recognizing conserved motifs present in pathogen-associated components and, in turn, activate the appropriate defense pathway. Toll-like receptors (TLRs) are one class of receptors that recognize pathogen-associated components. To date, ten TLRs have been discovered, each of which recognizes different ligands. TLR-9 recognizes unmethylated CpG dinucleotide motifs, which are prevalent in bacterial and viral DNAs, but are suppressed and methylated in vertebrate genomes. The immune system responds to the various CpG motifs by activating potent Th1-like immune responses.

The invention is based on the surprising finding that modulation of TLR-9 level or activity affects the onset and progression of autoimmune conditions. Specifically, the inventors have shown that administration of nucleic acids containing unmethylated CpG motifs prevents the onset of arthritis and significantly reduces the severity of arthritis in a well-characterized animal model. CpG can also halt the progression of arthritis already in progress. These results are surprising and unexpected because the intraarticular administration of CpG oligos had previously been shown to induce arthritis in various mouse models (Deng et al., (1999) Nature Medicine 5: 702), and because other reports showed that stimulation of the TLR-4 receptor enhances arthritis (Choe etal., (2003) J.Exp. Med. 197: 537-542). Clinical & Commercial Utility: The invention comprises compositions and methods for treating, reducing or preventing autoimmune conditions, particularly including arthritis. Specifically, compositions which include unmethylated CpG motifs, or other agents that are capable of activating the TLR-mediated immune response, can be used to treat, prevent or reduce the severity of autoimmune conditions.
Joslin Diabetes Center is the owner of U.S. Patent Numbers:

Type of Offer: Licensing

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