METHODS FOR THE TREATMENT OF DANON DISEASE AND OTHER DISORDERS OF AUTOPHAGY

1 . A gene therapy vector comprising an expression cassette comprising a polynucleotide encoding one or more isoforms of lysosome-associated membrane protein 2 (LAMP-2).

2 . The gene therapy vector of claim 1 , wherein the vector is a viral vector from a virus selected from the group consisting of adenovirus, retrovirus, lentivirus, herpesvirus, and adeno-associated virus (AAV).

3 . The gene therapy vector of claim 2 , wherein the vector is from one or more of adeno-associated virus (AAV) serotypes 1-11, or any subgroups thereof.

4 . The gene therapy vector of claim 2 , wherein the viral vector is encapsulated in an anionic liposome.

5 . The gene therapy vector of claim 1 , wherein the vector is a non-viral vector selected from the group consisting of naked DNA, a cationic liposome complex, a cationic polymer complex, a cationic liposome-polymer complex, and an exosome.

6 . The gene therapy vector of claim 1 , wherein the expression cassette comprises operably linked in the 5′ to 3′ direction, a first inverse terminal repeat, an enhancer/promoter region, the polynucleotide encoding one or more isoforms of LAMP-2, a 3′ untranslated region including a polyadenylation signal, and a second inverse terminal repeat.

7 . The gene therapy vector of claim 6 , wherein the promoter is selected from the group consisting of cytomegalovirus (CMV) promoter and CAG promoter.

8 . The gene therapy vector of claim 1 , wherein the polynucleotide comprises DNA or cDNA.

9 . The gene therapy vector of claim 1 , wherein the polynucleotide encoding one or more isoforms of LAMP-2 comprises one or more human LAMP-2 isoforms.

10 . The gene therapy vector of claim 1 , wherein the polynucleotide encoding one or more isoforms of LAMP-2 comprises one or more LAMP-2 isoforms selected from the group consisting of LAMP-2A, LAMP-2B, and LAMP-2C.

11 . The gene therapy vector of claim 1 , wherein the polynucleotide encoding one or more isoforms of LAMP-2 has at least about 90% sequence identity to one or more of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3.

12 . The gene therapy vector of claim 11 , wherein the polynucleotide encoding one or more isoforms of LAMP-2 comprises one or more of SEQ ID NO:1, SEQ ID NO:2, and SEQ ID NO:3.

13 . A method of preventing, mitigating, ameliorating, reducing, inhibiting, eliminating, and/or reversing one or more symptoms of Danon disease or another autophagy disorder in a subject in need thereof, comprising administering to the subject a gene therapy vector of claim 1 .

14 . A method of preventing, mitigating, ameliorating, reducing, inhibiting, eliminating, and/or reversing one or more symptoms of Danon disease or another autophagy disorder in a subject in need thereof, comprising administering to the subject an adeno-associated virus (AAV) vector comprising an expression cassette comprising a polynucleotide encoding one or more isoforms of lysosome-associated membrane protein 2 (LAMP-2).

15 . The method of claim 13 , wherein the vector is administered via a route selected from the group consisting of intravenous, intra-arterial, intracardiac, intracoronary, intramyocardial, intrarenal, intraurethral, epidural, and intramuscular.

16 . The method of claim 13 , wherein the vector is administered multiple times.

17 . The method of claim 13 , wherein the autophagy disorder is selected from the group consisting of end-stage heart failure, myocardial infarction, drug toxicities, diabetes, end-stage renal failure, and aging.

18 . The method of claim 13 , wherein the subject is exhibiting symptoms of Danon disease or another autophagy disorder.

19 . The method of claim 13 , wherein the subject has been identified as having reduced or non-detectable LAMP-2 expression.

20 . The method of claim 13 , wherein the subject has been identified as having a mutated LAMP-2 gene.