Institut National De La Sante Et De La Recherche Medicale

Association Institut De Myologie

Other

Centre National De La Recherche Scientifique

Sorbonne Université

Université Pierre Et Marie Curie (Paris 6)

Genethon

Royal Holloway and Bedford New College

The United States of America, as Represented by the Secretary, Department of Health and Human Services

Ucl Business Plc

Ruprecht-Karls-Universitat Heidelberg

Universitât Bern

Universitatsklinikum Hamburg-Eppendorf

Université Pierre Et Marie Curie

Inserm (Institut National De La Sante Et De La Recherche Medicale)

Thomas Voit

Luis Garcia

Thomas Eschenhagen

Christian Leumann

George Dickson

Caroline Le Guiner

Denis Furling

Philippe Moullier

Julie Dumonceaux

Cyriaque Beley

Giulia Mearini

Lucie Carrier

Virginie Mariot

Doreen Stimpel

Julia Mourot-Filiatre

Robert Michael Kotin

Matthew Wood

Martine Barkats

Graham McClorey

Fedor Svinartchouk

Lina Li

Stéphanie Lorain

Oliver Mueller

Daniel Schumperli

Maria-Grazia Biferi

Jérôme Denard

The present invention relates to a gene therapy vector which is useful in the treatment or prevention of hypertrophic cardiomyopathy in a subject in need thereof. The gene therapy vector of the invention comprises a nucleic acid sequence encoding a cardiac sarcomeric protein and a cardiomyocyte-specific promoter which is operably linked to said nucleic acid sequence. The invention furthermore relates to a cell which comprises the gene therapy vector. Pharmaceutical compositions which comprise the gene therapy vector and/or a cell comprising said vector are also provided. In another aspect, the invention relates to a method for treating or preventing hypertrophic cardiomyopathy in a subject by introducing the gene therapy vector of the invention into a subject in need of treatment.

Gene-therapy vectors for treating cardiomyopathy

The present invention provides a method for determining whether a patient will respond to treatment with a myostatin pathway inhibitor, the method comprising: (a) determining a level of myostatin and/or activin type II receptor (ActRII) and/or follistatin in at least one muscle biopsy obtained from a treatment target muscle in a subject having or suspected of having muscle atrophy or a muscle wasting condition; and (b) determining a level of myostatin and/or follistatin in a systemic sample obtained from the patient, wherein if: (i) the level of myostatin in the systemic sample is higher than a threshold and/or if the level of follistatin in the sample is lower than a threshold; and (ii) the level of myostatin and/or ActRII receptor in the at least one biopsy sample is higher than a threshold level and/or if the level of follistatin in the at least one biopsy sample is lower than a threshold level, the patient will respond to treatment.

Method relating to myostatin pathway inhibition

A composition comprising a gene therapy product for use in the treatment of a dystrophic disease in a subject, advantageously in humans, wherein:

Efficient systemic treatment of dystrophic muscle pathologies

The invention relates to a method for the treatment of amyotrophic lateral sclerosis (ALS). Specifically, the invention implements the use of an antisense sequence adapted to affect alternative splicing in a human SOD1 pre-mRNA, thereby leading to the destruction of the skipped m RNA by the cell machinery.

Treatment of amyotrophic lateral sclerosis

The present invention relates to the combined use of antisense oligonucleotides and viral vectors for the treatment of Duchenne muscular dystrophy.

Combined therapy for duchenne muscular dystrophy

Provided are tricyclo-DNA (tc-DNA) AON and methods employing tc-DNA AON for modifying splicing events that occur during pre-mRNA processing. Tricyclo-DNA (tc-DNA) AON are described that may be used to facilitate exon skipping or to mask intronic silencer sequences and/or terminal stein-loop sequences during pre-mRNA processing and to target RNase-mediated destruction of processed mRNA. Tc-DNA AON described herein may be used in methods for the treatment of Duchenne Muscular Dystrophy by skipping a mutated exon 23 or exon 51 within a dystrophin gene to restore functionality of a dystrophin protein; in methods for the treatment of Spinal Muscular Atrophy by masking an intronic silencing sequence and/or a terminal stem-loop sequence within an SMN2 gene to yield modified functional SMN2 protein, including an amino acid sequence encoded by exon 7, which is capable of at least partially complementing a non-functional SMN1 protein; and in methods for the treatment of Steinert's Myotonic Dystrophy by targeting the destruction of a mutated DM1 mRNA comprising 3'-terminal CUG repeats.

Tricyclo-DNA antisense oligonucleotides, compositions, and methods for the treatment of disease

The present invention relates to nucleic acids, compositions and methods for the treatment of facioscapulohumeral dystrophy.

Treatment of facioscapulohumeral dystrophy

A composition comprising a gene therapy product for use in the treatment of a dystrophic disease in a subject, advantageously in humans, wherein: &#x2014;the gene therapy product comprises a nucleic acid sequence encoding a functional microdystrophin; &#x2014;the composition is systemically administered.

The present invention relates to a nucleic acid molecule containing a sequence of tricyclo nucleosides joined by internucleoside phosphorothioate linkage. The invention also relates to synthetic antisense oligonucleotides and to methods employing the same.

Tricyclo-phosphorothioate DNA

An isolated linear nucleic acid molecule comprising in this order: a first adeno-associated virus (AAV) inverted terminal repeat (ITR), a nucleotide sequence of interest and a second AAV ITR, wherein said nucleic acid molecule is devoid of AAV capsid protein coding sequences. The said nucleic acid molecule can be applied to a host at repetition without eliciting an immune response. Methods for producing and purifying this nucleic acid molecule, and use of the same for therapeutic purposes are also provided.

Capsid-free AAV vectors, compositions, and methods for vector production and gene delivery

Methods for increasing the efficiency of target tissue penetration of an adeno-associated virus (AAV) vector in a patient are provided. In some aspects, the methods involve inhibiting the interaction of the serum protein galectin 3 binding protein (G3BP) with AAV vector. Further provided are methods for reducing tissue distribution of a virus or for neutralizing a virus harbored by an organ destined for transplant, or newly transplanted, by administering a composition comprising G3BP.

Methods of increasing efficiency of vector penetration of target tissue

The present invention relates to a method to improve the activity of engineered U7 snRNAs used in the context of RNA-based therapeutics; particularly in exon skipping, exon inclusion, and mRNA eradication strategies. The resulting modified U7 snRNAs are useful for treating neuromuscular diseases, in particular Duchenne neuromuscular dystrophy, myotonic dystrophy DM1 and spinal muscular atrophy.

Modified U7 snRNAs for treatment of neuromuscular diseases

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London, United Kingdom

Thomas Voit