Shire Human Genetic Therapies, Inc.

Takeda Pharmaceutical Company Limited

Jing Pan

Pericles Calias

Zahra Shahrokh

Teresa Leah Wright

Richard Pfeifer

Lawrence Charnas

Gaozhong Zhu

Thomas Mccauley

Kris Lowe

Jan Powell

Katherine Taylor

Paul Campolieto

James Christian

Nazila Salamat-Miller

Michael F Concino

Ray Yin

Angela Norton

Muthuraman Meiyappan

Bettina Strack-Logue

Bohong Zhang

Kevin Holmes

Andrea Iskenderian

Farah Natoli

Jennifer Terew

Yuan Jiang

Jamie Tsung

Brian Vernaglia

Paolo Martini

Dujie Qin

Yubei Zhang

Dianna Lundberg

Alla Romashko

Huang Yan

Mary Alessandrini

Yun Yen

Sujit Basu

Richard L Fahrner

Bingsen Zhou

Keethkumar Jain

Jianwen Feng

Rick Fahrner

Richard Fahmer

Richard Fahrner

Angela W Norton

Yan Huang

The present invention provides an effective and less invasive approach for direct delivery of therapeutic agents to the central nervous system (CNS). In some embodiments, the present invention provides methods including a step of administering intrathecally to a subject suffering from or susceptible to a lysosomal storage disease associated with reduced level or activity of a lysosomal enzyme, a composition comprising a replacement enzyme for the lysosomal enzyme.

CNS delivery of therapeutic agents

The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an arylsulfatase A (ASA) protein, salt, and a polysorbate surfactant for the treatment of Metachromatic Leukodystrophy Disease.

Methods and compositions for CNS delivery of arylsulfatase A

The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising a heparan N-sulfatase (HNS) protein, salt, and a polysorbate surfactant for the treatment of Sanfilippo Syndrome Type A.

Methods and compositions for CNS delivery of heparan N-sulfatase

The present invention provides, among other things, compositions and methods for CNS delivery of lysosomal enzymes for effective treatment of lysosomal storage diseases. In some embodiments, the present invention includes a stable formulation for direct CNS intrathecal administration comprising an iduronate-2-sulfatase (I2S) protein, salt, and a polysorbate surfactant for the treatment of Hunters Syndrome.

Methods and compositions for CNS delivery of iduronate-2-sulfatase

Methods and compositions for CNS delivery of heparan n-sulfatase

Among other things, the present invention provides methods and compositions of treating Sanfilippo syndrome type B (Sanfilippo B) by, e.g., intrathecal (IT) administration of a Naglu protein. A suitable Naglu protein can be a recombinant, gene-activated or natural protein. In some embodiments, a suitable Naglu protein is a recombinant Naglu protein. In some embodiments, a recombinant Naglu protein is a fusion protein containing a Naglu domain and a lysosomal targeting moiety. In some embodiments, the lysosomal targeting domain is an IGF-II moiety.

Therapeutic fusion protein comprising an alpha-n-acetylglucosaminidase and a lysosomal targeting moiety

The present invention provides, among oilier things, compositions and methods for CNS delivery of lysosomal enzymes (e.g., recombinant human arylsulfatase A (rhASA)) for effective treatment of lysosomal storage diseases (e.g. Metachromatic Leukodystrophy Disease), In some embodiments, the present invention includes a stable formulation for intrathecal administration comprising an ASA protein and a poloxamer, wherein less than 3% of the ASA protein exists in aggregated form.

Stable formulations for CNS delivery of arylsulfatase A

The invention provides compositions and methods for effective lysosomal targeting mediated by SORT1. In particular, the compositions and methods provided by the invention may be used to treat lysosomal storage diseases such as Sanfilippo syndrome type B.

Lysosomal targeting and uses thereof

Treatment of Sanfilippo syndrome type B by intrathecal administration of alpha-n-acetylglucosaminidase

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Boxborough, MA, United States of America

Jing Pan