Duke University

National University of Singapore

Sorbonne Université

Genethon

Dwight D Koeberl

Priya Kishnani

Suhrad G Banugaria

Sean N Prater

Baodong Sun

Paul M Yen

Benjamin L Farah

Andrea Amalfitano

Aravind Asokan

Federico Mingozzi

Giuseppe Ronzitti

Bradley Lowell Hodges

Arsen Hunanyan

Sang-Oh Han

Mohamad Mikati

Ram Puranam

Boris Kantor

Bradley L Hodges

The present invention relates, in general, to a method of treating patients undergoing enzyme replacement therapy (ERT) or other therapy involving the administration of a proteinaceous therapeutic agent as well gene replacement therapy with non-viral or viral vectors, or other therapeutic modality or modalities, used alone or in combination, which involve the administration of exogenous substances for potential therapeutic benefit, including, but not limited to DNA vaccines, siRNA, splice-site switching oligomers (SSOs) as well as RNA-based nanoparticles (RNPs) and nanovaccines. The invention further relates to compounds and compositions suitable for use in such methods.

Method of reducing titers of antibodies specific for a therapeutic agent

The present disclosure is directed to methods of treating a steatosis- associated disorder 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 and compositions for the treatment of steatosis-associated disorders

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 present disclosure provides nucleic acid expression cassettes, vectors, compositions and methods for the treatment of ATPase-mediated diseases in a subject.

Compositions comprising nucleic acid molecules and methods of treating ATPase-mediated diseases

The present disclosure is directed to methods of treating a steatosis-associated disorder 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.

The present invention relates, in general, to Pompe disease and, in particular, to a methods of treating Pompe disease and to compounds/constructs suitable for use in such methods.

Immunomodulating gene therapy

The present invention relates to variants of acid-alpha glucosidase and uses thereof. Said variants are sequence-optimized and/or are linked to a heterogenous signal peptide.

Acid-alpha glucosidase variants and uses thereof

The present disclosure is directed to methods of treating a steatosis-associated disorder 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 la, GSD lb, GSD Ic, NAFLD, and NASH. Other embodiments are directed to methods of reversing steatosis, modulating autophagy, inducing autophagy, and reversing glycogen storage.

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.

Growing community of inventors

Durham, NC, United States of America

Dwight D Koeberl