METHODS FOR TREATING CERVICAL DYSTONIA
This invention provides methods to treat or prevent cervical dystonia, a disorder related thereto, or a symptom thereof, with novel injectable compositions comprising botulinum toxin that may be administered to a subject suffering from such maledy. The injectable compositions and methods in which these compositions are used provide novel and advantageous treatments which result in high responder rates and long duration of effect, for example, a duration of effect for 24 weeks and longer.
1 . A method of treating cervical dystonia in an individual, the method comprising:
administering by injection a treatment dose of a sterile injectable composition into one or more of the muscles causing the cervical dystonia in the individual in need of treatment to achieve the therapeutic effect;
wherein the composition comprises a pharmaceutically acceptable diluent suitable for injection and a botulinum toxin of serotype A and 150 kD;
wherein the total treatment dose of botulinum toxin component administered to the individual is 100 U to 500 U;
wherein the composition comprises a positively charged carrier having a positively charged backbone of polylysine having covalently attached to each end a positively charged efficiency groups having an amino acid sequence selected from (gly) p -RGRDDRRQRRR-(gly) q (SEQ ID NO: 1), (gly) p -YGRKKRRORRR-(gly) q (SEQ ID NO: 2) or (gly) p -RKKRRQRRR-(gly) q (SEQ ID NO: 3), wherein the subscripts p and q are each independently an integer of from 0 to 20;
wherein the one or more muscles comprise at least one of sternocleidomastoid levator scapulae, and scalenus complex and wherein the sternocleidomastoid, levator scapulae, and scalenus complex are only unilaterally injected, and
wherein the therapeutic effect is associated with a risk of adverse events, risk of dysphagia, risk of musculoskeletal pain, and/or risk of muscular weakness that is below 15%.
2 . (canceled)
3 . The method of claim 1 , wherein the one or more muscles comprise sternocleidomastoid, levator scapulae, and scalenus complex.
4 . The method according to claim 1 , wherein the dose range for the sternocleidomastoid, levator scapulae, and scalenus complex is set forth in Table 1 or Table 6.
5 . A method of treating cervical dystonia in an individual, the method comprising:
administering by injection a treatment dose of a sterile injectable composition into one or more of the muscles causing the cervical dystonia in the individual in need of treatment to achieve the therapeutic effect;
wherein the composition comprises a pharmaceutically acceptable diluent suitable for injection; and a botulinum toxin of serotype A and 150 kD;
wherein the total treatment dose of botulinum toxin component administered to the individual is 100 U to 500 U;
wherein the composition comprises a positively charged carrier having a positively charged backbone of polylysine having covalently attached to each end a positively charged efficiency group having an amino acid sequence selected from (gly) p -RGRDDRRQRRR-(gly) q (SEQ ID NO: 1), (gly) p -YGRKKRRORRR-(gly) q (SEQ ID NO: 2) or (gly) p -RKKRRQRRR-(gly) q (SEQ ID NO: 3), wherein the subscripts p and q are each independently an integer of from 0 to 20; and
wherein the one or more muscles are selected from a group comprising or consisting of splenius capitis, splenius cervices, trapezius, longissimus, sternocleidomastoid, levator scapulae, and scalenus complex, wherein the dose range for each of the one or more muscles is set forth in Table 1 or Table 6; and
wherein the therapeutic effect is associated with a risk of adverse events, risk of dysphagia, risk of musculoskeletal pain, and/or risk of muscular weakness that is below 15%.
6 . (canceled)
7 . The method of claim 5 , wherein the sternocleidomastoid, levator scapulae, and scalenus complex are only unilaterally injected.
8 . The method according to claim 1 , wherein the risk of adverse events is less than 12%, 10%, 8%, 7%, 5%, or 3%.
9 . (canceled)
10 . The method of claim 1 , wherein (i) the subscripts p and q are each independently an integer of from 0 to 8; or (ii) are each independently an integer of from 2 to 5.
11 . (canceled)
12 . The method of claim 10 , wherein the positively charged carrier has the amino acid sequence RKKRRQRRRG-(K) 15 -GRKKRRQRRR (SEQ ID NO: 4).
13 . (canceled)
14 . (canceled)
15 . The method according to claim 1 , wherein the treatment dose of botulinum toxin is administered to the individual in an amount of about 100 U to 200 U or 125 U.
16 . The method according to claim 1 , wherein the treatment dose of botulinum toxin is administered to the individual in an amount of about 200 U to 300 U or 250 U.
17 . The method according to claim 1 , wherein the treatment dose of botulinum toxin is administered to the individual in an amount of 300 U to 450 U or 300 U.
18 . (canceled)
19 . (canceled)
20 . (canceled)
21 . The method according to claim 1 , wherein the duration of treatment effect comprises at least 16 weeks.
22 . The method according to claim 1 , wherein the duration of treatment effect comprises at least 20 weeks.
23 . The method according to claim 1 , wherein the duration of treatment effect comprises at least 22 weeks.
24 . The method according to claim 1 , wherein the duration of treatment effect comprises at least 24 weeks
25 . The method according to claim 1 , wherein the duration of treatment effect comprises at least 26 weeks
26 . (canceled)
27 . (canceled)
28 . The method according to claim 1 , wherein the risk of dysphagia from the treatment is less than 12%, 10%, 8%, 7%, 5%, or 3%.
29 . The method according to claim 1 , wherein the risk of musculoskeletal pain from the treatment is less than 12%, 10%, 8%, 7%, 5%, or 3%.
30 . The method according to claim 1 , wherein the risk of muscular weakness from the treatment is less than 12%, 10%, 8%, 7%, 5%, or 3%.