Treatment of neurological disorders by dsRNA administration
View Patent ↗The present invention relates to methods to treat neurological disorders comprising intrathecal injection of an effective amount of a double-stranded (ds) RNA into a subject in need, wherein the dsRNA inhibits the expression of a target gene and to pharmaceutical compositions useful for such treatment.
1. A method to treat or ameliorate pain in a subject in need thereof, the method comprising the step of intrathecal injection of an effective amount of a siRNA into the subject, wherein said siRNA inhibits the expression of the Mob-5 gene or an ortholog thereof by an RNA interference mechanism, and wherein more than 180 μg of siRNA per 120-140 grams of body weight per day are intrathecally injected.
2. A method according to claim 1 , wherein the subject is human and the ortholog is human.
3. A method according to claim 1 , wherein the subject is rat.
4. A method according to claim 1 , wherein said pain is chronic pain.
5. A method according to claim 4 , wherein said chronic pain is selected from the group consisting of cancer pain, osteoarthritis pain, allodynia and hyperalgesia.
6. A method according to claim 1 , wherein at least 200 μg of siRNA per 120-140 grams of body weight per day are intrathecally injected.
7. A method according to claim 1 , wherein the siRNA comprises a double-stranded region of 15 to 25 nt.
8. A method according to claim 1 , wherein the siRNA comprises a 3′ overhang on the antisense or the sense strand, or both strands, of at least one nucleotide.
9. A method according to claim 8 , wherein the overhang contains at least one modified nucleotide.
10. A method according to claim 8 , wherein the overhang comprises at least one 2′-MOE modified nucleotide.
11. A method according to claim 8 , wherein the overhang comprises 4 Uracils.
12. A method according to claim 1 , wherein the siRNA comprises at least one phosphorothioate linkage.
13. A method of reducing the expression of the Mob-5 gene or an ortholog thereof in a subject in need thereof, the method comprising the step of intrathecal injection of an effective amount of a siRNA into the subject inhibits the expression of the Mob-5 gene or an ortholog thereof by an RNA interference mechanism, and wherein more than 180 μg of siRNA per 120-140 grams of body weight per day are intrathecally injected.
14. The method of claim 13 , wherein the subject is human and the ortholog is human.
15. The method of claim 13 , wherein the subject is rat.
16. The method according to claim 13 , wherein said pain is chronic pain.
17. The method according to claim 16 , wherein said chronic pain is selected from the group consisting of cancer pain, osteoarthritis pain, allodynia and hyperalgesia.
18. The method according to claim 13 , wherein the siRNA comprises a 3′ overhang on the antisense or the sense strand, or both strands, of at least one nucleotide.
19. The method according to claim 18 , wherein the overhang contains at least one modified nucleotide.
20. The method according to claim 18 , wherein the overhang comprises at least one 2′-MOE modified nucleotide.
21. The method according to claim 18 , wherein the overhang comprises 4 Uracils.
22. The method according to claim 13 , wherein the siRNA comprises at least one phosphorothioate linkage.