Ptc Therapeutics, Inc.

F. Hoffmann-la Roche Ag

Sergey Paushkin

Ellen Welch

Nikolai A Naryshkin

Emmanuel Pinard

Hasane Ratni

Gary Mitchell Karp

Guangming Chen

Xiaoyan Zhang

Soongyu Choi

Hongyan Qi

Nanjing Zhang

Marla L Weetall

Jana Narasimhan

Anthony A Turpoff

Anuradha Bhattacharyya

Amal Dakka

Matthew G Woll

Xin Zhao

Chang-Sun Lee

Tianle Yang

Chunshi Li

Meenal Patel

Song Xiao Huang

Bansri S Furia

Love Volkova

Christopher Robert Trotta

Charles Romfo

Song Huang

Nikolai Naryshkin

Provided herein are compounds, compositions thereof and uses therewith for treating spinal muscular atrophy. In a specific embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN2 into mRNA that is transcribed from the SMN2 gene. In another specific embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN1 into mRNA that is transcribed from the SMN1 gene. In yet another embodiment, provided herein are compounds of a form that may be used to modulate the inclusion of exon 7 of SMN1 and SMN2 into mRNA that is transcribed from the SMN1 and SMN2 genes, respectively.

Compounds for treating spinal muscular atrophy

The present invention provides compounds and assays for the identification and validation of compounds for use in the treatment of spinal muscular atrophy (SMA), in which said compounds up-regulate the post-transcriptional expression of SMN1 or SMN2.

Survival motor neuron gene (SMN2) mRNA constructs for post-transcription regulation

Described herein are methods for the identification or validation of compounds capable of causing ribosomal frameshifting and the use of the compounds identified by the methods described herein to produce a stabilized SMN&#x394;Ex7 protein and treat Spinal Muscular Atrophy.

Methods for treating spinal muscular atrophy

The present invention relates to compounds that modulate ribosomal frameshifting and nucleic acid constructs for use in methods for identifying or validation of compounds that modulate ribosomal frameshifting. In particular, the present invention relates to the use of nucleic acid constructs to identify or validate compounds capable of modulating the efficiency of programmed ribosomal frameshifting and the use of compounds that modulate the efficiency of programmed ribosomal frameshifting to inhibit the replication or infectivity of viruses that employ programmed ribosomal frameshifting.

Screening assays for compounds that modulate programmed ribosomal frameshifting

The present invention provides nucleic acid constructs, methods for identifying and validating compounds that increase the inclusion of exon 7 of SMN2 into mRNA transcribed from the SMN2 gene, compounds and pharmaceutical compositions that increase levels of SMN protein produced from the SMN2 gene, and methods for use thereof in treating of SMA.

Methods of screening for compounds for treating spinal muscular atrophy using SMN mRNA translation regulation

The invention provides human protein complexes with endonuclease activity, including tRNA splicing endonuclease activity and 3' end pre-mRNA endonuclease activity, and pre-ribosomal RNA cleavage activity. The invention also provides a splice variant of human Sen2, and human protein complexes comprising the variant. The invention provides human protein complexes with pre-ribosomal RNA cleavage activity. The invention also provides antibodies that immunospecifically bind to a complex described herein or a component thereof, and uses of such antibodies. The present invention also provides methods of preparing and purifying the complexes and uses of the complexes inter alia, in screening, diagnosis, and therapy. The present invention further provides methods of identifying a compound that modulates the expression of a component of a complex described herein, the formation of a complex described herein or the activity of a complex described herein, and methods of preventing, treating, managing or ameliorating a disorder, such as a proliferative disorder, or a symptom thereof utilizing such a compound.

RNA processing protein complexes and uses thereof

Growing community of inventors

Belle Mead, NJ, United States of America

Sergey Paushkin