PEPTIDES AND METHODS OF TREATING DYSTROPHY-RELATED DISORDERS USING THE SAME
The disclosure relates to a pharmaceutical composition comprising any one or combination of PIF peptides or analogs or pharmaceutically acceptable salts thereof. Methods of treating a dystrophy-related disorder using the one or a combination of PIF peptide or analogs thereof or pharmaceutically acceptable salts thereof are also disclosed.
1 . A method of treating or preventing a dystrophin-related disorder in a subject in need thereof, the method comprising administering to the subject at least one pharmaceutical composition comprising:
a therapeutically effective amount of a pre-implantation factor (PIF) peptide, mimetics thereof, analogs thereof, or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable carrier.
2 . The method of claim 1 , wherein the pharmaceutically acceptable carrier is sterile and pyrogen-free water or sterile and pyrogen-free Lactated ringer's solution.
3 . The method of claim 1 , wherein the therapeutically effective dose is about 1.0 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
4 . The method of claim 1 , wherein the therapeutically effective dose is about 2.0 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
5 . The method of claim 1 , wherein the therapeutically effective dose is about 3.0 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
6 . The method of claim 1 , wherein the therapeutically effective dose is about 4.0 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
7 . The method of claim 1 , wherein the therapeutically effective dose is about 0.2 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
8 . The method of any of claim 1 , wherein the therapeutically effective dose is about 0.3 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
9 . The method of any of claim 1 , wherein the therapeutically effective dose is about 0.4 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
10 . The method of any of claim 1 , wherein the therapeutically effective dose is about 0.5 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
12 . The method of any of claim 1 , wherein the therapeutically effective dose is about 0.6 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
13 . The method of any of claim 1 , wherein the therapeutically effective dose is about 0.7 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
14 . The method of any of claim 1 , wherein the therapeutically effective dose is about 0.8 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
15 . The method of claim 1 , wherein the step of administering to the subject at least one PIF peptide, or a mimetic, analog, or pharmaceutically acceptable salt thereof comprises administering a therapeutically effective dose of the at least one PIF peptide thereof, or a mimetic, analog, or pharmaceutically acceptable salt thereof.
16 . The method of claim 1 , the PIF peptide is one or a combination of any one or plurality of: SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6 SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO:14, SEQ ID NO:15, SEQ ID NO:16, SEQ ID NO:17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, and/or SEQ ID NO:29, or pharmaceutically acceptable salt thereof.
17 . The method of claim 1 , the PIF peptide is SEQ ID NO:1 or a pharmaceutically acceptable salt thereof.
18 . The method of claim 1 , the PIF peptide is SEQ ID NO:2 or a pharmaceutically acceptable salt thereof.
19 . The method of claim 1 , the PIF peptide is SEQ ID NO:3 or a pharmaceutically acceptable salt thereof.
20 . The method of claim 1 , the PIF peptide is SEQ ID NO:4 or a pharmaceutically acceptable salt thereof.
21 . The method of claim 1 , the PIF peptide is SEQ ID NO:5 or a pharmaceutically acceptable salt thereof.
22 . The method of claim 1 , the PIF peptide is SEQ ID NO:6 or a pharmaceutically acceptable salt thereof.
23 . The method of claim 1 , the PIF peptide is SEQ ID NO:7 or a pharmaceutically acceptable salt thereof.
24 . The method of claim 1 , the PIF peptide is SEQ ID NO:8 or a pharmaceutically acceptable salt thereof.
25 . The method of claim 1 , the PIF peptide is SEQ ID NO:9 or a pharmaceutically acceptable salt thereof.
26 . The method of claim 1 , the PIF peptide is SEQ ID NO:10 or a pharmaceutically acceptable salt thereof.
27 . The method of claim 1 , the PIF peptide is SEQ ID NO: 11 or a pharmaceutically acceptable salt thereof.
28 . The method of claim 1 , the PIF peptide is SEQ ID NO:12 or a pharmaceutically acceptable salt thereof.
29 . The method of claim 1 , the PIF peptide is SEQ ID NO:13 or a pharmaceutically acceptable salt thereof.
30 . The method of claim 1 , the PIF peptide is SEQ ID NO:14 or a pharmaceutically acceptable salt thereof.
31 . The method of claim 1 , the PIF peptide is SEQ ID NO:15 or a pharmaceutically acceptable salt thereof.
32 . The method of claim 1 , the PIF peptide is SEQ ID NO:16 or a pharmaceutically acceptable salt thereof.
33 . The method of claim 1 , the PIF peptide is SEQ ID NO:17 or a pharmaceutically acceptable salt thereof.
34 . The method of claim 1 , the PIF peptide is SEQ ID NO:18 or a pharmaceutically acceptable salt thereof.
35 . The method of claim 1 , the PIF peptide is SEQ ID NO:19 or a pharmaceutically acceptable salt thereof.
36 . The method of claim 1 , the PIF peptide is SEQ ID NO:20 or a pharmaceutically acceptable salt thereof.
37 . The method of claim 1 , the PIF peptide is SEQ ID NO:21 or a pharmaceutically acceptable salt thereof.
38 . The method of claim 1 , the PIF peptide is SEQ ID NO:22 or a pharmaceutically acceptable salt thereof.
39 . The method of claim 1 , the PIF peptide is SEQ ID NO:23 or a pharmaceutically acceptable salt thereof.
40 . The method of claim 1 , the PIF peptide is SEQ ID NO:24 or a pharmaceutically acceptable salt thereof.
41 . The method of claim 1 , the PIF peptide is SEQ ID NO:25 or a pharmaceutically acceptable salt thereof.
42 . The method of claim 1 , the PIF peptide is SEQ ID NO:26 or a pharmaceutically acceptable salt thereof.
43 . The method of claim 1 , the PIF peptide is SEQ ID NO:27 or a pharmaceutically acceptable salt thereof.
44 . The method of claim 1 , the PIF peptide is SEQ ID NO:28 or a pharmaceutically acceptable salt thereof.
45 . The method of claim 1 , the PIF peptide is SEQ ID NO:29 or a pharmaceutically acceptable salt thereof.
46 . The method of claim 1 , wherein the step of administering to the subject at least one PIF peptide, or mimetic, analog or pharmaceutically acceptable salt thereof comprises administering a therapeutically effective dose of the PIF peptide, or mimetic, analog or pharmaceutically acceptable salt thereof from about 0.001 mg/kg to about 200 mg/kg.
47 . The method of claim 1 , wherein the step of administering to the subject at least one PIF peptide, or mimetic, analog or pharmaceutically acceptable salt thereof, comprises administering a therapeutically effective dose of the PIF peptide, or mimetic, analog or pharmaceutically acceptable salt thereof from about 0.5 mg/kg to about 5 mg/kg.
48 . The method of any of claims 1 - 47 , wherein the at least the PIF peptide, or mimetic, analog or pharmaceutically acceptable salt thereof comprises a chemical targeting moiety and/or a radioactive moiety.
49 . The method of claim 48 , wherein the at least one PIF peptide, or mimetic, analog or pharmaceutically acceptable salt thereof comprises at least one radioactive moiety comprising at least one or a combination of the following isotopes: 2 H, 3 H, 13 C, 14 C, 15 N, 16 O, 17 O, 31 P, 32 P, 35 S, 18 F, and 36 Cl.
50 . The method of any of claims 1 - 49 , wherein the method further comprises administering at least one analgesic and/or one anti-inflammatory compound.
51 . The method of claim 50 , wherein the method further comprises administering at least one analgesic and or one anti-inflammatory compound before, after, or simultaneously with the administration of a therapeutically effective dose of at least one PIF peptide, or mimetic, analog or pharmaceutically acceptable salt thereof.
52 . The method of any of claims 1 - 51 , wherein the pharmaceutical composition further comprises a therapeutically effective dose of one or a plurality of active agents.
53 . The method of claim 52 , wherein the one or plurality of active agents is one or a combination of compounds chosen from: an anti-inflammatory compound, alpha-adrenergic agonist, antiarrhythmic compound, analgesic compound, and an anesthetic compound.
54 . The method of any of claims 1 - 53 , wherein the pharmaceutical composition is free of SEQ ID NO: 1 or a pharmaceutically acceptable salt thereof.
55 . A method of improving the clinical outcome in a subject suffering with, diagnosed with or suspected of having a dystrophin-related disorder comprising administering to the subject at least one pharmaceutical composition comprising:
a therapeutically effective amount of a pre-implantation factor (PIF) peptide, an analog thereof, or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable carrier.
56 . The method of any of claims 1 - 55 , wherein the pharmaceutical composition is administered via parenteral injection, subcutaneous injection, intravenous injection, intramuscular injection, intraperitoneal injection, transdermally, orally, buccally, ocular routes, intravaginally, by inhalation, by depot injections, or by implants.
57 . The method of any of claims 1 - 55 , wherein the pharmaceutical composition further comprises one or combination of active agents is selected from Table Y.
58 . The method of either of claim 1 or 55 , wherein the method further comprises administration of one or a plurality of compositions comprising active agents selected from Table Y sequentially or contemporaneously.
59 . A method administering to the subject at least one pharmaceutical composition comprising a therapeutically effective amount of a PIF peptide, mimetics thereof, analogs thereof, or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.
60 . A method of treating or preventing muscle degeneration in a subject in need thereof, the method comprising administering to the subject at least one pharmaceutical composition comprising:
a therapeutically effective amount of a pre-implantation factor (PIF) peptide, mimetics thereof, analogs thereof, or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable carrier.
61 . The method of claim 60 , wherein the pharmaceutically acceptable carrier is sterile and pyrogen-free water or sterile and pyrogen-free Lactated ringer's solution.
62 . The method of claim 60 , wherein the therapeutically effective dose is about 1.0 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
63 . The method of claim 60 , wherein the therapeutically effective dose is about 2.0 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
64 . The method of claim 60 , wherein the therapeutically effective dose is about 3.0 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
65 . The method of claim 60 , wherein the therapeutically effective dose is about 4.0 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
66 . The method of claim 60 , wherein the therapeutically effective dose is about 0.2 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
67 . The method of any of claim 60 , wherein the therapeutically effective dose is about 0.3 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
68 . The method of any of claim 60 , wherein the therapeutically effective dose is about 0.4 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
69 . The method of any of claim 60 , wherein the therapeutically effective dose is about 0.5 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
70 . The method of any of claim 60 , wherein the therapeutically effective dose is about 0.6 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
71 . The method of any of claim 60 , wherein the therapeutically effective dose is about 0.7 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
72 . The method of any of claim 60 , wherein the therapeutically effective dose is about 0.8 mg/kg, wherein kg is kilograms of the subject and mg is milligrams of the therapeutically effective dose.
73 . The method of claim 60 , wherein the step of administering to the subject at least one PIF peptide, or a mimetic, analog, or pharmaceutically acceptable salt thereof comprises administering a therapeutically effective dose of the at least one PIF peptide thereof, or a mimetic, analog, or pharmaceutically acceptable salt thereof.
74 . The method of claim 60 , the PIF peptide is one or a combination of any one or plurality of: SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6 SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, and/or SEQ ID NO:29, or pharmaceutically acceptable salt thereof.
75 . The method of claim 60 , the PIF peptide is SEQ ID NO:1 or a pharmaceutically acceptable salt thereof.
76 . The method of claim 60 , the PIF peptide is SEQ ID NO:2 or a pharmaceutically acceptable salt thereof.
77 . The method of claim 60 , the PIF peptide is SEQ ID NO:3 or a pharmaceutically acceptable salt thereof.
78 . The method of claim 60 , the PIF peptide is SEQ ID NO:4 or a pharmaceutically acceptable salt thereof.
79 . The method of claim 60 , the PIF peptide is SEQ ID NO:5 or a pharmaceutically acceptable salt thereof.
80 . The method of claim 60 , the PIF peptide is SEQ ID NO:6 or a pharmaceutically acceptable salt thereof.
81 . The method of claim 60 , the PIF peptide is SEQ ID NO:7 or a pharmaceutically acceptable salt thereof.
82 . The method of claim 60 , the PIF peptide is SEQ ID NO:8 or a pharmaceutically acceptable salt thereof.
83 . The method of claim 60 , the PIF peptide is SEQ ID NO:9 or a pharmaceutically acceptable salt thereof.
84 . The method of claim 60 , the PIF peptide is SEQ ID NO: 10 or a pharmaceutically acceptable salt thereof.
85 . The method of claim 60 , the PIF peptide is SEQ ID NO:11 or a pharmaceutically acceptable salt thereof.
86 . The method of claim 60 , the PIF peptide is SEQ ID NO: 12 or a pharmaceutically acceptable salt thereof.
87 . The method of claim 60 , the PIF peptide is SEQ ID NO: 13 or a pharmaceutically acceptable salt thereof.
88 . The method of claim 60 , the PIF peptide is SEQ ID NO: 14 or a pharmaceutically acceptable salt thereof.
89 . The method of claim 60 , the PIF peptide is SEQ ID NO: 15 or a pharmaceutically acceptable salt thereof.
90 . The method of claim 60 , the PIF peptide is SEQ ID NO: 16 or a pharmaceutically acceptable salt thereof.
91 . The method of claim 60 , the PIF peptide is SEQ ID NO: 17 or a pharmaceutically acceptable salt thereof.
92 . The method of claim 60 , the PIF peptide is SEQ ID NO: 18 or a pharmaceutically acceptable salt thereof.
93 . The method of claim 60 , the PIF peptide is SEQ ID NO: 19 or a pharmaceutically acceptable salt thereof.
94 . The method of claim 60 , the PIF peptide is SEQ ID NO:20 or a pharmaceutically acceptable salt thereof.
95 . The method of claim 60 , the PIF peptide is SEQ ID NO:21 or a pharmaceutically acceptable salt thereof.
96 . The method of claim 60 , the PIF peptide is SEQ ID NO:22 or a pharmaceutically acceptable salt thereof.
97 . The method of claim 60 , the PIF peptide is SEQ ID NO:23 or a pharmaceutically acceptable salt thereof.
98 . The method of claim 60 , the PIF peptide is SEQ ID NO:24 or a pharmaceutically acceptable salt thereof.
99 . The method of claim 60 , the PIF peptide is SEQ ID NO:25 or a pharmaceutically acceptable salt thereof.
100 . The method of claim 60 , the PIF peptide is SEQ ID NO:26 or a pharmaceutically acceptable salt thereof.
101 . The method of claim 60 , the PIF peptide is SEQ ID NO:27 or a pharmaceutically acceptable salt thereof.
102 . The method of claim 60 , the PIF peptide is SEQ ID NO:28 or a pharmaceutically acceptable salt thereof.
103 . The method of claim 60 , the PIF peptide is SEQ ID NO:29 or a pharmaceutically acceptable salt thereof.
104 . The method of claim 60 , wherein the step of administering to the subject at least one PIF peptide, or mimetic, analog or pharmaceutically acceptable salt thereof comprises administering a therapeutically effective dose of the PIF peptide, or mimetic, analog or pharmaceutically acceptable salt thereof from about 0.001 mg/kg to about 200 mg/kg.
105 . The method of claim 60 , wherein the step of administering to the subject at least one PIF peptide, or mimetic, analog or pharmaceutically acceptable salt thereof, comprises administering a therapeutically effective dose of the PIF peptide, or mimetic, analog or pharmaceutically acceptable salt thereof from about 0.5 mg/kg to about 5 mg/kg.
106 . The method of any of claims 1 - 105 , wherein the subject is human.
107 . A method of treating or preventing fibrosis in a subject in need thereof, the method comprising administering to the subject at least one pharmaceutical composition comprising:
a therapeutically effective amount of a PIF peptide, mimetics thereof, analogs thereof, or a pharmaceutically acceptable salt thereof; and
a pharmaceutically acceptable carrier.
108 . The method of claim 107 , wherein the fibrosis is muscle fibrosis.
109 . The method of claim 107 , the PIF peptide is one or a combination of any one or plurality of: SEQ ID NO: 1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6 SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, and/or SEQ ID NO:29, or pharmaceutically acceptable salt thereof.
110 . The method of claim 107 , wherein the step of administering to the subject at least one PIF peptide, or mimetic, analog or pharmaceutically acceptable salt thereof comprises administering a therapeutically effective dose of the PIF peptide, or mimetic, analog or pharmaceutically acceptable salt thereof from about 0.001 mg/kg to about 200 mg/kg.