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 P 2 X 3 gene 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 said pain is chronic neuropathic pain.
3. A method according to claim 2 wherein said chronic pain is selected from the group consisting of cancer pain, osteoarthritis pain, allodynia and hyperalgesia.
4. A method according to claim 1 wherein the subject in need is a human.
5. A method according to claim 1 wherein the subject in need is a rat.
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 to treat or ameliorate pain in a subject in need thereof, wherein the method comprises the step of intrathecal injection into the subject of an effective amount of a composition comprising a siRNA targeting the gene P 2 X 3 , wherein the siRNA targets a P 2 X 3 gene sequence corresponding to that of a double-stranded RNA having any of the sequences of SEQ ID NOs: 7-10 or 13-16, wherein the composition inhibits the expression of the P 2 X 3 gene by an RNA interference mechanism.
14. The method according to claim 13 , wherein said pain is chronic neuropathic pain.
15. The method according to claim 14 , wherein said chronic pain is selected from the group consisting of cancer pain, osteoarthritis pain, allodynia and hyperalgesia.
16. 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, wherein said siRNA inhibits the expression of the P 2 X 3 gene by an RNA interference mechanism, and wherein the dosage of siRNA is more than 180 μg of siRNA per 120-140 grams of body weight per day.
17. The method according to claim 16 , wherein said pain is chronic neuropathic pain.
18. The method according to claim 17 , wherein said chronic pain is selected from the group consisting of cancer pain, osteoarthritis pain, allodynia and hyperalgesia.
19. The method according to claim 16 , wherein the subject in need is a human.
20. The method according to claim 16 , wherein the siRNA comprises a double-stranded region of 15 to 25 nt.
21. The method according to claim 16 , wherein the siRNA comprises a 3′ overhang on the antisense or the sense strand, or both strands, of at least one nucleotide.
22. The method according to claim 21 , wherein the overhang contains at least one modified nucleotide.
23. The method according to claim 21 , wherein the overhang comprises at least one 2′-MOE modified nucleotide.
24. The method according to claim 21 , wherein the overhang comprises 4 Uracils.
25. The method according to claim 16 , wherein the siRNA comprises at least one phosphorothioate linkage.