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 the administration of a bioactive agent selected from Hsp70; a functional fragment of Hsp70 or variant thereof having at least 95% sequence identity to Hsp70, to an individual in need thereof.
2 . The method according to claim 1 , wherein said bioactive agent is formulated as a pharmaceutical composition.
3 . The method according to claim 1 , wherein said Hsp70, or functional fragment or variant thereof, has 100% identity to wild-type Hsp70 protein.
4 . The method according to claim 1 , wherein said bioactive agent is Hsp70.
5 . The method according to claim 1 , wherein said Hsp70 is full length Hsp70
6 . The method according to claim 1 , wherein said bioactive agent is a functional fragment or variant of Hsp70 having at least 95% sequence identity to Hsp70.
7 . The method according to claim 1 , wherein said functional fragment or variant of Hsp70 comprises all or part of the ATPase domain of Hsp70.
8 . The method according to claim 1 , wherein said functional fragment or variant of Hsp70 comprises tryptophan at amino acid position 90 of the Hsp70 ATPase domain.
9 . The method according to claim 1 , wherein said Hsp70, or a functional fragment or variant thereof, is recombinant Hsp70 (rHsp70).
10 . The method according to claim 1 , wherein said Hsp70 is derived from a mammal selected from the group consisting of human ( homo sapiens ), mouse ( mus musculus ), cow, dog, rat, ferret, pig, sheep, and monkey.
11 . The method according to claim 1 , wherein said treatment is curative or ameliorating.
12 . The method according to claim 1 , wherein said treatment is administered prior to onset of the disease.
13 . The method according to claim 1 , wherein said lysosomal storage disease is Fabry disease.
14 . The method according to claim 1 , wherein said lysosomal storage disease is selected from the group consisting of Fabry disease, Farber disease, Krabbe disease, Fabry disease, Gaucher disease, Sialidosis, Metachromatic leukodystrophy and saposin-deficiency.
15 . The method according to claim 1 , wherein said lysosomal storage disease is selected from the group consisting of a lipid storage disorder (lipidoses) including sphingolipidoses, gangliosidoses and leukodystrophies; mucopolysaccharidoses, glycoprotein storage disorders (glucoproteinoses) and mucolipidoses.
16 . 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, a bioactive agent capable of increasing the intracellular concentration of Hsp70, and a bioactive agent capable of amplifying Hsp70 gene expression which is a hydroxylamine derivative.
17 . The method according to claim 1 , wherein said bioactive agent is administered in combination with enzyme replacement therapy (ERT).
18 . The method according to claim 19 , wherein said enzyme replacement therapy is selected from the group consisting of imiglucerase, miglustat, agalsidase beta and agalsidase alpha.
19 . The method according to claim 1 , wherein said bioactive agent is administered to an individual in need thereof by parenteral administration or enteral administration; wherein said parenteral administration is selected from the group consisting of intravenous, intra-arterial, intramuscular, intracardiac, subcutaneous, intraosseous, intradermal, intrathecal, intraspinal, intraperitoneal, transdermal, transmucosal, insufflation, sublingual, buccal, vaginal, inhalational, intranasal, epidural, intravitreal and topical administration; and wherein said enteral administration is selected from the group consisting of oral administration and intrarectal administration.
20 . The method according to claim 1 , wherein said bioactive agent is administered at a dosage of 1 microgram to 100 milligram per kilogram body weight.