HMGB1 variants and uses thereof
The present invention relates to HMGB1 variants that maintain HMGB1 wild type chemoattractant function while displaying abolished cytokine and/or chemokine stimulating properties. Such molecules are useful in therapy.
1. A method for treating injured skeletal muscle or fractured bone in a subject in need thereof, the method comprising administering to the subject an amount of a High Mobility Group Box 1 (HMGB1) variant effective to promote healing of injured skeletal muscle or fractured bone, wherein the variant HMGB1 consists of SEQ ID NO: 1, wherein cysteine residues at positions 23, 45, and 106 of SEQ ID NO: 1 are replaced by serine residues.
2. The method of claim 1 , wherein the HMGB1 variant is a cell chemoattractant that does not stimulate cytokine and/or chemokine production from a cell.
3. The method of claim 1 , wherein the HMGB1 variant will not induce TNF expression in macrophages.
4. The method of claim 1 , wherein the HMGB1 variant is administered to the subject systemically.
5. The method of claim 1 , wherein the HMGB1 variant is administered to the subject by local injection to the muscle or bone to be treated.
6. A method for limiting damage to muscle in a subject having muscle that has been injured, comprising administering to the subject an effective amount of a High Mobility Group Box 1 (HMGB1) variant, wherein the variant HMGB1 consists of SEQ ID NO: 1, wherein cysteine residues at positions 23, 45, and 106 of SEQ ID NO: 1 are replaced by serine residues.
7. The method of claim 6 , wherein the HMGB1 variant is administered to the subject by local injection to the muscle.
8. The method of claim 6 , wherein the HMGB1 variant is administered to the subject systemically.
9. The method of claim 6 , wherein the muscle is skeletal muscle.