Abstract: Adult form glycogen storage disease type III (GSD III) is an orphan neuromuscular disorder caused by a deficiency of glycogen debranching enzyme. Long-term complications include progressive liver fibrosis, hepatic failure, and end-stage liver cirrhosis, and progressive muscle myopathy. Presently, there are no clinically approved therapies or cures for GSD III. Disclosed herein are compositions for and methods of treating and/or preventing GSD III disease progression.

Abstract: This disclosure provides isolated nucleic acid molecules comprising nucleic acid sequences encoding microbial polypeptides that are codon optimized for expression in mammalian cells, vectors comprising an immunotolerant dual promoter system, and methods using these polynucleotides and polypeptides to treat glycogen storage diseases and other inherited diseases.

Abstract: The disclosure relates, in general, to Glycogen Storage Disease and, in particular, to a method of treating Glycogen Storage Disease and to compounds and compositions suitable for use in such a method.

Abstract: The present disclosure is directed to methods of treating a steatosis-associated disorder and methods of treating a cytoplasmic glycogen storage disorder, including glycogen storage disease I, glycogen storage disease III, glycogen storage disease IV, and/or conditions associated with a PRKAG2 mutation, by administering a therapeutic agent selected from a lysosomal enzyme, an autophagy-inducing agent, or a combination thereof. Steatosis-associated disorders discussed herein include GSD Ia, GSD Ib, GSD Ic, NAFLD, and NASH. Other embodiments are directed to methods of reversing steatosis, modulating autophagy, inducing autophagy, and reversing glycogen storage. Methods of treating a cytoplasmic glycogen storage disorder by administering a lysosomal enzyme and a second therapeutic agent are also described. Other embodiments are directed to methods of treating a cytoplasmic glycogen storage disorder by administering a therapeutic agent as an adjunctive therapy to lysosomal enzyme replacement therapy.

Abstract: The disclosure relates, in general, to Glycogen Storage Disease Type VI and, in particular, to a method of treating Glycogen Storage Disease Type VI and to compounds and compositions suitable for use in such a method.

Abstract: The disclosure relates, in general, to Glycogen Storage Disease and, in particular, to a method of treating Glycogen Storage Disease and to compounds and compositions suitable for use in such a method.

Abstract: The disclosure relates, in general, to Glycogen Storage Disease and, in particular, to a method of treating Glycogen Storage Disease Type IX and to compounds and compositions suitable for use in such a method, including acid alpha-glucosidase.

Abstract: Provided are isolated nucleic acids for expressing lysosomal polypeptides such as lysosomal acid ?-glucosidase (GAA) and vectors comprising the same. In one embodiment, the invention provides an isolated nucleic acid encoding a chimeric polypeptide comprising a secretory signal sequence operably linked to a lysosomal polypeptide. In another representative embodiment, an isolated nucleic acid is provided comprising a coding region encoding a GAA and a GAA 3? untranslated region (UTR), wherein the GAA 3? UTR comprises a deletion therein. In another representative embodiment, the invention provides an isolated nucleic acid comprising a coding region encoding a GAA and a 3? UTR, wherein the 3? UTR is less than about 200 nucleotides in length and comprises a segment that is heterologous to the GAA coding region.

Abstract: The present disclosure is directed to methods of treating a cytoplasmic glycogen storage disorder, including glycogen storage disease I, glycogen storage disease III, glycogen storage disease IV, and/or conditions associated with a PRKAG2 mutation, by administering a lysosomal enzyme such as acid alpha-glucosidase. Conditions associated with a PRKAG2 mutation may include hypotonia, cardiomyopathy, myopathy, cytoplasmic glycogen accumulation, ventricular hypertrophy, severe infantile hypertrophic cardiomyopathy, heart rhythm disturbances, increased left ventricular wall thickness, ventricular pre-excitation, or a combination thereof. Methods of treating a cytoplasmic glycogen storage disorder by administering a lysosomal enzyme and a second therapeutic agent are also described. Other embodiments are directed to methods of treating a cytoplasmic glycogen storage disorder by administering a therapeutic agent as an adjunctive therapy to lysosomal enzyme replacement therapy.

Abstract: The present disclosure provides compositions and methods for improving the efficacy of enzyme replacement therapy for lysosomal storage diseases.

Abstract: The disclosure relates, in general, to Glycogen Storage Disease and, in particular, to a method of treating Glycogen Storage Disease and to compounds and compositions suitable for use in such a method.

Abstract: Provided are isolated nucleic acids for expressing lysosomal polypeptides such as lysosomal acid ?-glucosidase (GAA) and vectors comprising the same. The invention provides an isolated nucleic acid encoding a chimeric polypeptide comprising a secretory signal sequence operably linked to a lysosomal polypeptide. The invention also provides an isolated nucleic acid comprising a coding region encoding a GAA and a GAA 3? untranslated region (UTR), wherein the GAA 3? UTR comprises a deletion therein. The invention further provides an isolated nucleic acid comprising a coding region encoding a GAA and a 3? UTR wherein the 3? UTR is less than about 200 nucleotides in length and comprises a segment that is heterologous to the GAA coding region. Also provided are methods of making and using delivery vectors encoding lysosomal polypeptides to produce the lysosomal polypeptide to treat subjects afflicted with a deficiency in the lysosomal polypeptide.

Abstract: The disclosure relates, in general, to Glycogen Storage Disease and, in particular, to a method of treating Glycogen Storage Disease and to compounds and compositions suitable for use in such a method.

Abstract: The disclosure relates, in general, to Glycogen Storage Disease and, in particular, to a method of treating Glycogen Storage Disease and to compounds and compositions suitable for use in such a method.

Abstract: The present invention relates, in general, to Glycogen Storage Disease and, in particular, to a method of treating Glycogen Storage Disease-type-III and to compounds and compositions suitable for use in such a method.

Abstract: Provided are isolated nucleic acids for expressing lysosomal polypeptides such as lysosomal acid ?-glucosidase (GAA) and vectors comprising the same. The invention provides an isolated nucleic acid encoding a chimeric polypeptide comprising a secretory signal sequence operably linked to a lysosomal polypeptide. The invention also provides an isolated nucleic acid comprising a coding region encoding a GAA and a GAA 3? untranslated region (UTR), wherein the GAA 3? UTR comprises a deletion therein. The invention further provides an isolated nucleic acid comprising a coding region encoding a GAA and a 3? UTR wherein the 3? UTR is less than about 200 nucleotides in length and comprises a segment that is heterologous to the GAA coding region. Also provided are methods of making and using delivery vectors encoding lysosomal polypeptides to produce the lysosomal polypeptide to treat subjects afflicted with a deficiency in the lysosomal polypeptide.

Abstract: A recombinant hybrid virus, including: (a) a deleted adenovirus vector genome comprising the adenovirus 5? and 3? cis-elements for viral replication and encapsidation, and further comprising a deletion in an adenovirus genomic region selected from the group consisting of: (i) the polymerase region, wherein said deletion essentially prevents the expression of a functional polymerase protein from said deleted region and said hybrid virus does not otherwise express a functional polymerase protein, (ii) the preterminal protein region, wherein said deletion essentially prevents the expression of a functional preterminal protein from said deleted region, and said hybrid virus does not otherwise express a functional preterminal protein, and (iii) both the regions of (i) and (ii); and (b) a recombinant adeno-associated virus (AAV) vector genome flanked by the adenovirus vector genome sequences of (a), said recombinant AAV vector genome comprising (i) AAV 5? and 3? inverted terminal repeats, (ii) an AAV packaging sequ

Abstract: The present invention relates, in general, to Glycogen Storage Disease and, in particular, to a method of treating Glycogen Storage Disease-type-III and to compounds and compositions suitable for use in such a method.

Abstract: A recombinant hybrid virus which includes: (a) a deleted adenovirus vector genome having the adenovirus 5? and 3? cis-elements for viral replication and encapsidation and a deletion in an adenovirus genomic region selected from the polymerase region and/or the preterminal protein region, wherein the deletion essentially prevents the expression of a functional polymerase and/or preterminal protein from the deleted region and the hybrid virus does not otherwise express a functional polymerase protein; and (b) a recombinant adeno-associated virus (AAV) vector genome flanked by the adenovirus vector genome sequences of (a), wherein the recombinant AAV vector genome includes an AAV packaging sequence and a heterologous nucleic acid sequence, wherein the heterologous nucleic acid sequence is flanked by 5? and 3? AAV inverted terminal repeats.

Abstract: A recombinant hybrid virus, including: (a) a deleted adenovirus vector genome comprising the adenovirus 5? and 3? cis-elements for viral replication and encapsidation, and further comprising a deletion in an adenovirus genomic region selected from the group consisting of: (i) the polymerase region, wherein said deletion essentially prevents the expression of a functional polymerase protein from said deleted region and said hybrid virus does not otherwise express a functional polymerase protein, (ii) the preterminal protein region, wherein said deletion essentially prevents the expression of a functional preterminal protein from said deleted region, and said hybrid virus does not otherwise express a functional preterminal protein, and (iii) both the regions of (i) and (ii); and (b) a recombinant adeno-associated virus (AAV) vector genome flanked by the adenovirus vector genome sequences of (a), said recombinant AAV vector genome comprising (i) AAV 5? and 3? inverted terminal repeats, (ii) an AAV packaging sequ