Combined therapy for muscular diseases

Patent metadata

Field	Value
Publication number	US-2022387624-A1
Application number	US-202017774732-A
Country	US
Kind code	A1
Filing date	Nov 5, 2020
Priority date	Nov 6, 2019
Publication date	Dec 8, 2022
Grant date	—

Abstract

The present invention relates to the treatment of muscular diseases.

First claim

1 . A method for treating a muscular disease, comprising administering to a subject in need thereof a combination product comprising:
a GDF5 pathway-activating substance and at least one other active ingredient suitable for the treatment of the muscular disease.

2 . The method according to claim 1 , wherein the GDF5 pathway-activating substance is:
a vector comprising a gene encoding GDF5, such as human GDF5; or recombinant GDF5, such as recombinant human GDF5.

3 . The method according to claim 16 , wherein the at least one other active ingredient is the combination of (i) an antisense oligonucleotide (AON) capable of inducing an exon-skipping in a dystrophin pre-mRNA, and (ii) a viral vector, such as an AAV vector, encoding a Duchenne muscular dystrophy therapeutic product, wherein said component (i) is administered before administering component (ii).

4 . The method according to claim 3 , wherein the viral vector of component (ii) is either (a) coding an antisense oligonucleotide able to induce exon-skipping within a dystrophin pre-mRNA, (b) encoding dystrophin gene-editing means, or (c) coding a functional dystrophin protein.

5 . The method according to claim 3 , wherein said AON is a phophorodiamidate morpholino oligomer, such as a peptide-phosphorodiamidate morpholino oligomer, in particular a Pip6a-PMO oligomer.

6 . The method according to claim 3 , wherein said viral vector of component (ii) encodes an U7-AON.

7 . The method according to claim 3 , wherein said viral vector of component (ii) encodes a functional truncated dystrophin such as a mini- or micro-dystrophin.

8 . The method according to claim 3 , wherein the GDF5 pathway-activating substance is administered:
before administration of component (i); during administration of component (i); between administration of component (i) and administration of component (ii); during administration of component (ii); or after administration of component (ii).

9 . The method according to claim 17 , wherein the at least one other active ingredient is an antisense oligonucleotide (AON) capable of inducing an exon-skipping in the SOD1 pre-mRNA, thereby leading to the incorporation of a premature stop codon into the mature mRNA.

10 . The method according to claim 1 , wherein the at least one other active ingredient is a vector comprising a gene encoding a survival of motor neuron protein, such as the SMN1 or SMN2 gene.

11 . A kit comprising:
a GDF5 pathway-activating substance; and at least one other active ingredient.

12 . The kit according to claim 11 , wherein the at least one other active ingredient comprises:
an isolated AON capable of inducing an exon-skipping in a dystrophin pre-mRNA; and a Duchenne muscular dystrophy therapeutic viral vector.

13 . The kit according to claim 12 , wherein the Duchenne muscular dystrophy viral vector
encodes an antisense oligonucleotide able to induce exon-skipping within a dystrophin pre-mRNA; encodes a dystrophin gene-editing means; or encodes a functional dystrophin protein.

14 . The kit according to claim 11 , wherein the GDF5 pathway-activating substance is a vector, such as a plasmid or viral vector, in particular a viral vector, more particularly an AAV vector, comprising a gene encoding GDF5, in particular human GDF5.

15 . The kit according to claim 11 , wherein the GDF5 pathway-activating substance is recombinant GDF5, in particular recombinant human GDF5.

16 . The method of claim 1 , wherein the muscular disease is Duchenne muscular dystrophy.

17 . The method of claim 1 , wherein the muscular disease is amyotrophic lateral sclerosis.

Assignees

• Association Inst De Myologie
• Inst Nat Sante Rech Med
• Univ Sorbonne

Inventors

• Pietri-Rouxel France
• Falcone Sestina

Classifications

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• A61K48/005 Primary

  characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered · CPC title

• A61K31/713

  Double-stranded nucleic acids or oligonucleotides · CPC title

• C12N2320/31

  Combination therapy · CPC title

• C12N2310/11

  Antisense · CPC title