METHODS FOR SLOWING FAMILIAL ALS DISEASE PROGRESSION

• US 20120214865A1
• Filed: 02/27/2012
• Published: 08/23/2012
• Est. Priority Date: 06/21/2001
• Status: Active Grant

• Current Assignee: Ionis Pharmaceuticals, Inc.
• Original Assignee: ISIS Pharmaceuticals Incorporated
• Inventors: BENNETT, C. FRANK, FREIER, SUSAN M., DOBIE, KENNETH W.
• Granted Patent: US 8,921,331 B2
• Time in Patent Office: Days
• US Class Current: 514/44.A
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/3341 5-Methylcytosine
• CPC Class Codes: C12N 2310/341 Gapmers, i.e. of the type ===---===
• CPC Class Codes: C12N 2310/346 having a combination of backbone and sugar modifications
• CPC Class Codes: C12N 2310/3525 MOE, methoxyethoxy
• CPC Class Codes: C12Y 115/01001 Superoxide dismutase (1.15.1.1)
• CPC Class Codes: Y02P 20/582 Recycling of unreacted starting or intermediate materials

Abstract

Methods for slowing disease progression in an individual suffering from familial ALS are provided. Also provided are methods of increasing the survival time of an individual suffering from familial ALS. These methods employ antisense oligonucleotides targeted to SOD1, for use in inhibiting the expression of SOD1 in the central nervous system of an individual suffering from familial ALS.

Claims

1. A method of treating amyotrophic lateral sclerosis (ALS) comprising administering to the cerebrospinal fluid of a subject in need thereof a therapeutically or prophylactically effective amount of a composition comprising:

a modified oligonucleotide consisting of 12 to 30 linked nucleosides targeted to SOD-1, wherein the modified oligonucleotide is specifically hybridizable to SEQ ID NO;

1, and

a pharmaceutically acceptable diluent or carrier.

2. The method of claim 1, wherein administering is intrathecal administration.

3. The method of claim 1, wherein administering is intraventricular administration.

4. The method of claim 1, wherein at least one internucleoside linkage is a phosphorothioate internucleoside linkage.

5. The method of claim 1, wherein at least one nucleoside comprises a modified sugar.

6. The method of claim 5, wherein the modified sugar is a 2′

-O-methoxyethyl.

7. The method of claim 1, wherein at least one nucleoside comprises a modified nucleobase.

8. The method of claim 7, wherein the modified nucleobase is a 5-methylcytosine.

9. The method of claim 1, wherein the modified oligonucleotide comprises:

a gap segment consisting of linked deoxynucleosides;

a 5′

wing segment consisting of linked nucleosides;

a 3′

wing segment consisting of linked nucleosides;

wherein the gap segment is position between the 5′

wing segment and the 3′

wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.

10. The method of claim 9, wherein the modified oligonucleotide comprises:

a gap segment consisting of ten linked deoxynucleosides;

a 5′

wing segment consisting of five linked nucleosides;

a 3′

wing segment consisting of five linked nucleosides;

wherein the gap segment is position between the 5′

wing segment and the 3′

wing segment, wherein each nucleoside of each wing segment comprises a 2′

-O-methoxyethyl sugar;

wherein each cytosine is a 5′

methylcytosine, and wherein each internucleoside linkage is a phosphorothioate linkage.

11. A method of treating amyotrophic lateral sclerosis (ALS) comprising administering to the cerebrospinal fluid of a subject in need thereof a therapeutically or prophylactically effective amount of a composition comprising:

a modified oligonucleotide consisting of 12 to 30 linked nucleosides targeted to SOD-1, wherein the modified oligonucleotide is 100% complementary to SEQ ID NO;

1, and

a pharmaceutically acceptable diluent or carrier.

12. The method of claim 11, wherein administering is intrathecal administration.

13. The method of claim 11, wherein administering is intraventricular administration.

14. The method of claim 11, wherein at least one internucleoside linkage is a phosphorothioate internucleoside linkage.

15. The method of claim 11, wherein at least one nucleoside comprises a modified sugar.

16. The method of claim 15, wherein the modified sugar is a 2′

-O-methoxyethyl.

17. The method of claim 11, wherein at least one nucleoside comprises a modified nucleobase.

18. The method of claim 17, wherein the modified nucleobase is a 5-methylcytosine.

19. The method of claim 11, wherein the modified oligonucleotide comprises:

a gap segment consisting of linked deoxynucleosides;

a 5′

wing segment consisting of linked nucleosides;

a 3′

wing segment consisting of linked nucleosides;

wherein the gap segment is position between the 5′

wing segment and the 3′

wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.

20. The method of claim 19, wherein the modified oligonucleotide comprises:

a gap segment consisting of ten linked deoxynucleosides;

a 5′

wing segment consisting of five linked nucleosides;

a 3′

wing segment consisting of five linked nucleosides;

wherein the gap segment is position between the 5′

wing segment and the 3′

wing segment, wherein each nucleoside of each wing segment comprises a 2′

-O-methoxyethyl sugar;

wherein each cytosine is a 5′

methylcytosine, and wherein each internucleoside linkage is a phosphorothioate linkage.