Copolymers for suppression of autoimmune diseases, and methods of use
Random three- and four-amino acid copolymers having lengths of 14-, 35- and 50-amino acid residues are provided. The random copolymers have amino acids alanine, lysine and one or more of the hydrophobic amino acids valine, phenylalanine, tryptophan and tyrosine. Random three-amino acid copolymer FAK efficiently suppressed EAE induced in SJL/J (H-2S) mice with the encephalitogenic epitope PLP 139-151. Random four-amino acid copolymers VYAK and tryptophan-containing VWAK were efficacious in alleviating severity and duration of symptoms of EAE induced by MBP 85-99 (SEQ ID NO:2), in a humanized mouse model expressing genes for both an HLA-DR-2 linked to multiple sclerosis (MS) in humans and for a T cell receptor from an MS patient.
1. A linear random copolymer FAK comprising amino acids phenylalanine (F), alanine (A), and lysine (K), wherein the amino acids F:A:K are polymerized in a molar ration having a range of 1:5:3 to 1:10:3.
2. A random linear copolymer comprising amino acids alanine (A), lysine (K), and a plurality of hydrophobic amino acids selected from the group consisting of: valine (V), phenylalanine (F), tryptophan (W), and tyrosine (Y), providing that the copolymer is not YFAK.
3. A composition comprising a copolymer according to claim 2 in combination with at least one additional therapeutic agent.
4. A composition according to claim 3 , wherein the additional therapeutic agent is selected from the group of: an antibody, an enzyme inhibitor, an antibacterial, an antiviral, a steroid, a nonsteroidal anti-inflammatory, an antimetabolite, a cytokine, a cytokine blocking agent, an adhesion molecule blocking agent, and a soluble cytokine receptor.
5. A kit comprising at least one unit dosage of a random linear copolymer according to claim 2 .
6. A kit according to claim 5 , wherein the molar ratio in the copolymer of the amino acids A:K:(sum of the hydrophobic amino acids) has a range of about 5:3:1 to about 10:3:1.