Saint Louis University

Seikagaku Corporation

Kanazawa University

Jcr Pharmaceuticals Co., Ltd.

The Nemours Foundation

Shimane University

Shimadzu Corporation

Regenxbio Inc.

Shunji Tomatsu

William S Sly

Shuichi Miyaura

Adriana M Montaño-Suarez

Jeffrey H Grubb

Luis Barrera

Kazuo Okamura

Tatsuo Nishioka

Seiji Yamaguchi

Alan Knutsen

Ken'ichi Miyamoto

Clifford Bellone

Masamichi Yamada

Yasuhiro Tosaka

Angela Catalina Sosa-Molano

Ken-ichi Miyamoto

Mana Yamada

Jun Watanabe

Takanari Hattori

Adriana Maria Montano Suarez

Monica A Gutierrez

Amelia Ortigoza Rodriguez, Legal Representative

Carlos J Alméciga-Diaz

Olivier Danos

Subha Karumuthil-Melethil

Kazuki Sawamoto

Misa Tanaka

Tsutomu Shimada

Tetsuo Iida

Hironori Kobayashi

Provided herein are gene therapy methods for the treatment of mucopolysaccharidosis type IVA (MPS IVA) involving the use of recombinant adeno-associated viruses (rAAVs) to deliver human N-acetylgalactosamine-6-sulfate sulfatase (hGALNS) to the bone of a human subject diagnosed with MPS IVA. Also provided herein are rAAVs that can be used in the gene therapy methods and methods of making such rAAVs.

Treatment of mucopolysaccharidosis IVA

Provided is a method by which the disaccharides derived from glycosaminoglycans can be analyzed in a stable and highly reproducible manner. A method for analyzing a glycosaminoglycan according to the present invention includes: a first process for producing a plurality of kinds of disaccharides derived from a glycosaminoglycan in a biological sample by adding a plurality of kinds of glycosaminoglycan-specific enzymes to the biological sample; and a second process for separating and analyzing the plurality of kinds of disaccharides by a liquid chromatography-mass spectrometry method, where a column used for liquid chromatography in the liquid chromatography-mass spectrometry method is a column packed with a stationary-phase support to which an amide group as a functional group is bound, or a column packed with a stationary-phase support to which an adamantyl group as a functional group is bound.

Method for analyzing glycosaminoglycan

Disclosed are methods and compositions for determining immunodominant peptides of target enzymes used in enzyme replacement therapy for lysosomal storage disorders. More specifically disclosed are immunodominant peptides for N-acetylgalactosamine-6-sulfatase (GALNS). Also disclosed are methods of inducing oral tolerance towards a target enzyme through oral administration of immunodominant peptides prior to commencing enzyme replacement therapy. More specifically disclosed is a method of inducing oral tolerance for GALNS, by orally administering specific immunodominant peptides for GALNS; in subjects suffering from mucopolysaccharidosis type IVA prior to commencing enzyme replacement therapy using GALNS.

Method of treating mucopolysaccharidosis type IVA

Provided is a rapid screening method for detecting mucopolysaccharidosis IVA and mucopolysaccharidosis VII. Biological samples containing glycosaminoglycans are enzymatically digested to converts chondroitin 6-sulfate into &#x394;Di-6S. &#x394;Di-6S is assayed by liquid chromatography-tandem mass spectroscopy analysis. Elevated &#x394;Di-6S, and thus elevated chondroitin 6-sulfate present in the sample, indicates a likelihood that the test subject is afflicted with mucopolysaccharidosis IVA or mucopolysaccharidosis VII.

Mucopolysaccharidosis IVA/VII screening and treatment method

The present invention provides compositions and methods for use in enzyme replacement therapy. The inventors disclose a method of producing membrane bound enzymes in an active soluble form by eliminating the glycosylphosphatidylinositol (GPI) membrane anchor. In particular the inventors disclose a soluble active form of the membrane bound enzyme TNSALP which they produced by deleting the GPI anchor single peptide sequence. They have further shown that this composition is useful for treatment of hypophosphatasia. The inventors also disclose oligo acid amino acid variants thereof which specifically target bone tissue.

Compositions and methods for treating hypophosphatasia

A method for detecting lysosomal storage diseases including the steps of performing an assay for a single species of glycosaminoglycan contained in a specimen and correlating results of the assay with lysosomal storage diseases. A body fluid such as urine or blood can be employed as a specimen. The assay can be performed by use of a polypeptide that is capable of specifically binding to a glycosaminoglycan-containing molecule. The polypeptide may be an antibody, or a polypeptide having an antigen-binding site of an antibody.

Method for detecting lysosomal storage diseases

Disclosed are a fusion protein comprising enzyme N-acetylgalactosamine-6-sulfate sulfatase and a short peptide consisting of 4-15 acidic amino acids attached to the enzyme on its N-terminal side, a pharmaceutical composition containing the fusion protein, and a method for treatment of type A Morquio disease using the fusion protein. Compared with the native enzyme protein, the fusion protein exhibits higher transferability to bone tissues and improved, higher stability in the blood.

Proteins with an attached short peptide of acidic amino acids

The present invention provides a polypeptide therapeutic agent, useful in enzyme replacement therapy, with increased therapeutic benefits for the central nervous system. The invention provides a method of enhancing the effect of a polypeptide or protein on the central nervous system by the attachment of a short acidic amino acid sequence. Specifically the inventors disclose the attachment of a 4-15 acidic amino acid sequence to human &#x3b2;-glucuronidase by construction of a fusion protein. This molecule is useful in the treatment of type VII mucopolysaccharidosis when administered to a patient.

Enhancing the effect of therapeutic proteins on the central nervous system

This invention relates to compositions and methods of delivering therapeutic agents to bone. More specifically, the invention relates to endowing a large molecule vectors i.e., adeno virus, retrovirus, liposomes, micelles, natural and synthetic polymers, or combinations thereof, with the ability to target bone tissue in vivo and with improved stability in the blood, by attaching multiple copies of acid amino acid peptides. One preferred embodiment of the invention relates to endowing an adeno-associated virus (AAV) vector with the ability to target bone-tissue in vivo and improve its stability, by the addition of multiple acidic amino acid peptides attached to the capsid of the viral vector.

Delivery of therapeutic agents to the bone

Growing community of inventors

Wilmington, DE, United States of America

Shunji Tomatsu