Use of Hsp70 as a regulator of enzymatic activity
The present invention concerns a method for modulating the enzymatic activity of an enzyme, wherein said enzyme interacts with BMP, said method comprising the step of administering or inducing Hsp70, or a functional fragment or variant thereof, in a form suitable for allowing interaction between BMP and Hsp70, or said functional fragment or variant thereof, and thereby modulating the enzymatic activity of an enzyme interacting with BMP.
1. A method for treatment of mucopolysaccaridoses, glycoproteinoses, and mucolipidoses, comprising administering to an individual in need thereof a bioactive agent capable of increasing the intracellular concentration of Hsp70 by amplifying Hsp70 gene expression, wherein said bioactive agent is a hydroxylamine derivative.
2. The method according to claim 1 , wherein said treatment is curative or ameliorating.
3. The method according to claim 1 , wherein said hydroxylamine derivative is bimoclomol, or a structural analogue thereof.
4. The method according to claim 1 , wherein said hydroxylamine derivative is selected from the group consisting of bimoclomol, arimoclomol, and BGP-15.
5. The method according to claim 1 , wherein said hydroxylamine derivative is arimoclomol.
6. The method according to claim 1 , wherein said hydroxylamine derivative is BRX-345.
7. The method according to claim 1 , wherein said bioactive agent is administered in combination with at least one other treatment modality.
8. The method according to claim 7 , wherein said at least one one other treatment modality is individually selected from the group consisting of enzyme replacement therapy (ERT), pain relievers, corticosteroids, a transplantation, substrate reduction therapy, Hsp70 protein, a functional fragment of Hsp70 having at least 95% sequence identity to Hsp70, and a functional variant of Hsp70 having at least 95% sequence identity to Hsp70.
9. The method according to claim 1 , wherein said bioactive agent is administered in combination with enzyme replacement therapy (ERT).
10. The method according to claim 9 , wherein said enzyme replacement therapy is selected from the group consisting of imiglucerase, Miglustat, agalsidase beta and agalsidase alpha.
11. The method according to claim 8 , wherein said functional fragment or variant of Hsp70 comprises all or part of the ATPase domain of Hsp70.
12. The method according to claim 8 , wherein said Hsp70, or a functional fragment or variant thereof, is recombinant Hsp70 (rHsp70).
13. The method according to claim 1 , wherein said mucopolysaccharidoses comprise a disorder selected from the group consisting of Hunter syndrome and Hurler disease.
14. The method according to claim 1 , wherein said hydroxylamine derivative is BRX-220.