DNA methyltransferases for the treatment and prevention of arthritis
The present disclosure is directed to compositions and methods for treating osteoarthritis comprising increasing the expression of Dnmt3b and/or inhibiting aminobutyrate aminotransferase.
1. A method to reduce cartilage degradation in a human subject, the method comprising administering to the subject a composition comprising a compound that increases the expression of Dmnt3b and/or a compound that inhibits aminobutyrate aminotransferase.
2. The method of claim 1 , wherein the compound that increases the expression of Dmnt3b is a vector comprising the Dnmtb3nucleotide sequence.
3. The method of claim 1 , wherein the compound that inhibits aminobutyrate aminotransferase is selected from the group consisting of vigabatrin, L-2,4-diaminobutyric acid dihydrochloride, gamma-acetylenic GABA, S(+)-gamma-vinyl-GABA, 3-methyl-GABA, 4-amino-5-hexynoic acid, gabaculine, aminooxyacetic acid, phenelzine, phenylethylidenehydrazine (PEH),rosmarinic acid and valproic acid.
4. The method of claim 3 , wherein the compounds that inhibits aminobutyrate aminotransferase is vigabatrin.
5. The method of claim 1 , wherein the subject is at risk of developing osteoarthritis (OA).
6. The method of claim 5 , wherein the subject is obese or has had joint surgery.
7. The method of claim 1 , wherein the composition is administered orally or via intra-articular injection.
8. A method to increase cartilage area, the method comprising administering a composition comprising a compound that increases the expression of Dmnt3b and/or a compound that inhibits aminobutyrate aminotransferase.
9. The method of claim 8 , wherein the compound that increases the expression of Dmnt3b is a vector comprising the Dnmtb3nucleotide sequence.
10. The method of claim 8 , wherein the compound that inhibits aminobutyrate aminotransferase is selected from the group consisting of vigabatrin, L-2,4-diaminobutyric acid dihydrochloride, gamma-acetylenic GABA, S(+)-gamma-vinyl-GABA, 3-methyl-GABA, 4-amino-5-hexynoic acid, gabaculine, aminooxyacetic acid, phenelzine, phenylethylidenehydrazine (PEH), rosmarinic acid and valproic acid.
11. The method of claim 10 , wherein the compounds that inhibits aminobutyrate aminotransferase is vigabatrin.
12. The method of claim 8 , wherein the subject is at risk of developing osteoarthritis (OA).
13. The method of claim 8 , wherein the composition is administered orally or via intra-articular injection.
14. A method of treating osteoarthritis (OA) in a subject, the method comprising administering to the subject a composition comprising a compound that increases the expression of Dmnt3b and/or a compound that inhibits aminobutyrate aminotransferase.
15. The method of claim 14 , wherein the compound that increases the expression of Dmnt3b is a vector comprising the Dnmtb3nucleotide sequence.
16. The method of claim 14 , wherein the compound that inhibits aminobutyrate aminotransferase is selected from the group consisting of vigabatrin, L-2,4-diaminobutyric acid dihydrochloride, gamma-acetylenic GABA, S(+)-gamma-vinyl-GABA, 3-methyl-GABA, 4-amino-5-hexynoic acid, gabaculine, aminooxyacetic acid, phenelzine, phenylethylidenehydrazine (PEH), rosmarinic acid and valproic acid.
17. The method of claim 16 , wherein the compounds that inhibits aminobutyrate aminotransferase is vigabatrin.
18. The method of claim 14 , wherein the subject is at risk of developing OA.
19. The method of claim 14 , further comprising administering standard treatments for OA.
20. The method of claim 14 , wherein the composition is administered orally or via intra-articular injection.
21. A method to reduce cartilage degradation, the method comprising administering a composition comprising a compound that increases the expression of Dmnt3b and/or a compound that inhibits aminobutyrate aminotransferase,
wherein the compound is selected from the group consisting of vigabatrin, L-2,4-diaminobutyric acid dihydrochloride, gamma-acetylenic GABA, S(+)-gamma-vinyl-GABA, 3-methyl-GABA, 4-amino-5-hexynoic acid, gabaculine, aminooxyacetic acid, phenelzine, phenylethylidenehydrazine (PEH) and valproic acid.