Genzyme Corporation

Ionis Pharmaceuticals, Inc.

The Brigham and Women's Hospital, Inc.

Isis Pharmaceuticals, Inc.

Cold Spring Harbor Laboratory

Biogen Ma Inc.

Lamya S Shihabuddin

Seng H Cheng

Marco A Passini

Gene Hung

C Frank Bennett

Susan M Freier

Holly Kordasiewicz

Don W Cleveland

Lisa Stanek

James C Dodge

Michael Schlossmacher

Valerie Cullen

James Dodge

Catherine R O'Riordan

Frank Rigo

Adrian R Krainer

Katherine W Klinger

Yimin Hua

Abraham Scaria

Catherine R O'riordan

Lisa M Stanek

Sergio Pablo Sardi

Jennifer Sullivan

C Frank Bennet

Robin J Ziegler

Compositions and methods for treating disorders affecting motor function, such as motor function affected by disease or injury to the brain and/or spinal cord, are disclosed.

Gene therapy for neurodegenerative disorders

Provided herein are methods, compounds, and compositions for reducing expression of huntingtin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate Huntington's disease, or a symptom thereof.

Modulation of huntingtin expression

Provided herein are improved rAAV (e.g., rAAV2, rAAVrh8R, etc.) for enhanced gene therapy of ocular disorders or CNS disorders wherein the rAAV comprise one or more substitutions of amino acids that interact with heparan sulfate proteoglycan. The invention provides methods for improved transduction of retinal cells and methods for treating ocular diseases with improved compositions of rAAV particles. Further provided herein are improved recombinant adeno-associated virus (rAAV) (e.g., rAAV2, rAAVrh8R, etc.) for enhanced gene therapy of disorders of the CNS. The invention provides methods for delivering the rAAV to the CNS, methods for treating disorders of the CNS with improved compositions of rAAV particles, and kits for delivering the rAAV to the CNS and/or treating a CNS disorder.

AAV vectors for retinal and CNS gene therapy

This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention a transgene product is delivered to a subject's spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the brain. The viral vector delivers the transgene to a region of the brain which is susceptible to infection by the virus and which expresses the encoded recombinant viral gene product. Also provided are compositions for delivery of a transgene product to a subject's spinal cord by administering a recombinant neurotrophic viral vector containing the transgene to the subject's brain.

Gene therapy for amyotrophic lateral sclerosis and other spinal cord disorders

Modulation of Huntington expression

Neurological diseases, including lysosomal storage diseases, can be successfully treated using intraventricular delivery of the therapeutic agents to bypass the blood-brain barrier. Similarly, diagnostic agents and anesthetic agents can be delivered to the brain in this manner. The administration can be performed slowly to achieve maximum effect. Such administration permits greater penetration of distal portions of the brain.

Slow intraventricular delivery

The present provides methods for treating spinal muscular atrophy using a self-complementary recombinant adeno-associated virus (rAAV) viral particle comprising a transgene expressing SMN. In one aspect, the viral particles are administered the spinal column or cisterna magna in a human subject; for example, a pediatric human subject. Viral particles comprising AAV9 capsids are contemplated.

Compositions and methods for treating spinal muscular atrophy

This disclosure provides methods and compositions for treating disorders or injuries that affect motor function and control in a subject. In one aspect, the invention provides a method to deliver a transgene to a subject's spinal cord by administering a recombinant neurotropic viral vector containing the transgene. The viral vector delivers the transgene to a region of the deep cerebellar nuclei region of the brain. Also provided are compositions and methods to deliver a transgene to a subject's spinal cord by administering a recombinant neurotropic viral vector containing the transgene to the motor cortex region of the subject's brain.

Gene therapy for spinal cord disorders

This invention relates generally to treating synucleinopathies in subjects that are not clinically diagnosed with a lysosomal storage disease, as well as associated methods of making medicaments and screening methods.

Treatment of synucleinopathies

Growing community of inventors

West Newton, MA, United States of America

Lamya S Shihabuddin