Exon Skipping Therapy for Functional Amelioration of Semifunctional Dystrophin in Becker and Duchenne Muscular Dystrophy
First Claim
1. A method for treating a muscular dystrophy caused by instability of a semi-functional dystrophin in a patient in need thereof, comprising the step ofadministering to said patient antisense oligonucleotides complementary to nucleic acid sequences that are necessary for correct splicing of a region comprising or consisting of exon 42 of said semi-functional dystrophin.
1 Assignment
0 Petitions
Accused Products
Abstract
Methods for stabilizing unstable proteins or for restoring functionality to non-functional or poorly functioning (semi-functional) proteins using exon skipping technology are provided. The methods involve the administration of antisense oligonucleotides to cause exon skipping, thereby removing one or more exons responsible for protein instability or lack of functionality. For example, exons encoding protease recognition sites may be removed. The method is useful for treating diseases caused by protein instability, such as Becker Muscular Dystrophy, or for treating Duchenne Muscular Distrophy patients with semi-functional dystrophin due to treatment with other exon skipping or stop codon readthrough therapies.
66 Citations
22 Claims
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1. A method for treating a muscular dystrophy caused by instability of a semi-functional dystrophin in a patient in need thereof, comprising the step of
administering to said patient antisense oligonucleotides complementary to nucleic acid sequences that are necessary for correct splicing of a region comprising or consisting of exon 42 of said semi-functional dystrophin.
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12. A method of stabilizing a semi-functional dystrophin protein comprising the step of
preventing cleavage of said semi-functional dystrophin protein at a protease recognition site HPSS.
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15. An antisense oligonucleotide complementary to
nucleic acid sequences of exon 42 of dystrophin, or nucleic acid sequences adjacent to exon 42 which are required for correct splicing of exon 42 of dystrophin.
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17. A dystrophin protein selected from the group consisting of Δ
- 42, Δ
45-47 dystrophin protein;
Δ
42, Δ
45-48 dystrophin protein;
Δ
42, Δ
49-51 dystrophin protein; and
Δ
42, Δ
50-51 dystrophin protein.
- 42, Δ
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19-20. -20. (canceled)
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21. A method of manufacturing a medicament to treat a muscular dystrophy caused by instability of a semi-functional dystrophin, comprising the steps of
designing an antisense oligonucleotide complementary to nucleic acid sequences of exon 42 of dystrophin, or nucleic acid sequences adjacent to exon 42 which are required for correct splicing of exon 42 of dystrophin; -
synthesizing said antisense oligonucleotide; and combining said antisense oligonucleotide and a pharmaceutically or physiologically acceptable carrier to form said medicament. - View Dependent Claims (22)
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Specification