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 a lysosomal storage disease 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 treatment is administered prior to onset of the disease.
4. The method according to claim 1 , wherein said hydroxylamine derivative is bimoclomol, or a structural analogue thereof.
5. The method according to claim 1 , wherein said hydroxylamine derivative is selected from the group consisting of bimoclomol, arimoclomol, BRX-220, BRX-345 and BGP-15.
6. The method according to claim 1 , wherein said hydroxylamine derivative is arimoclomol.
7. The method according to claim 1 , wherein said hydroxylamine derivative is BRX-345.
8. The method according to claim 1 , wherein said lysosomal storage disease is selected from the group consisting of Niemann-Pick disease, Farber disease, Krabbe disease, Fabry disease, Gaucher disease, Sialidosis, Metachromatic leukodystrophy and saposin-deficiency.
9. The method according to claim 8 , wherein said Niemann-Pick disease is selected from the group consisting of Niemann-Pick disease type A, Niemann-Pick disease type B, Niemann-Pick disease type C and Niemann-Pick disease type D.
10. The method according to claim 1 , wherein said bioactive agent is administered in combination with at least one other treatment modality, wherein said at least 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.
11. The method according to claim 1 , wherein said bioactive agent is administered in combination with enzyme replacement therapy (ERT).
12. The method according to claim 11 , wherein said enzyme replacement therapy is selected from the group consisting of imiglucerase, Miglustat, agalsidase beta and agalsidase alpha.
13. The method according to claim 10 , wherein said functional fragment or variant of Hsp70 comprises all or part of the ATPase domain of Hsp70.
14. The method according to claim 10 , wherein said Hsp70, or a functional fragment or variant thereof, is recombinant Hsp70 (rHsp70).