Duke University

Baodong Sun

Priya Kishnani

Yuan-Tsong Chen

Dwight D Koeberl

Andrea Amalfitano

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.

Methods and compositions for the treatment of cytoplasmic glycogen storage disorders

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.

Method of treating glycogen storage disease type VI

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.

Method of treating glycogen storage disease type IX using acid alpha-glucosidase

Provided are isolated nucleic acids for expressing lysosomal polypeptides such as lysosomal acid &#x3b1;-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&#x2032; UTR comprises a deletion therein. The invention further provides an isolated nucleic acid comprising a coding region encoding a GAA and a 3&#x2032; UTR wherein the 3&#x2032; 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.

Constructs for expressing lysosomal polypeptides

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.

Methods for treating glycogen storage disease type IV usng lysosomal acid alpha-glucosidase

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.

Method of treating glycogen storage disease type III with human acid &#x3b1;-glucosidase

A recombinant hybrid virus which includes: (a) a deleted adenovirus vector genome having the adenovirus 5' and 3&#x2032; 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&#x2032; and 3&#x2032; AAV inverted terminal repeats.

Growing community of inventors

Durham, NC, United States of America

Baodong Sun