PEPTIDE THERAPEUTICS AND METHODS FOR USING SAME
Disclosed herein are methods and compositions for the treatment and/or prevention of diseases or conditions comprising administration of an MPP, and/or naturally or artificially occurring variants or analogues of an MPP, or pharmaceutically acceptable salts thereof, alone or in combination with one or more active agents (e.g., an aromatic-cationic peptide such as D-Arg-2′6′-Dmt-Lys-Phe-NH 2 ).
1 .- 27 . (canceled)
28 . A method for treating or preventing mitochondrial dysfunction, or a disease or condition characterized by mitochondrial dysfunction, in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a composition comprising the mitochondria penetrating peptide (MPP) Cha-Arg-Cha-Lys-NH2 alone or in combination with one or more aromatic-cationic peptides selected from the group consisting of:
2′6′-Dmp-D-Arg-2′6′-Dmt-Lys-NH 2 ;
2′,6′-Dmt-D-Arg-Phe-Lys-NH 2 ;
2′6′-Dmp-D-Arg-Phe-Lys-NH 2 ;
2′6′-Dmt-D-Arg-PheOrn-NH 2 ;
2′6′-Dmt-D-Arg-Phe-Ahp(2-aminoheptanoicacid)-NH 2 ;
2′6′-Dmt-D-Arg-Phe-Lys-NH 2 ;
2′6′-Dmt-D-Cit-PheLys-NH 2 ;
Ala-D-Phe-D-Arg-Tyr-Lys-D-Trp-His-D-Tyr-Gly-Phe;
Arg-D-Dmt-Arg-NH 2 ;
Arg-D-Dmt-Lys-NH 2 ;
Arg-D-Dmt-NH 2 ;
Arg-D-Leu-D-Tyr-Phe-Lys-Glu-D-Lys-Arg-D-Trp-Lys-D-Phe-Tyr-D-Arg-Gly;
Arg-D-Tyr-Arg-NH 2 ;
Arg-D-Tyr-Lys-NH 2 ;
Arg-D-Tyr-NH 2 ;
Asp-Arg-D-Phe-Cys-Phe-D-Arg-D-Lys-Tyr-Arg-D-Tyr-Trp-D-His-Tyr-D-Phe-Lys-Phe;
Asp-D-Trp-Lys-Tyr-D-His-Phe-Arg-D-Gly-Lys-NH 2 ;
D-Arg-2′6′-Dmt-Lys-Phe-NH 2 ;
D-Arg-Arg-Dmt-Phe-NH 2 ;
D-Arg-Arg-Tyr-Phe-NH 2 ;
D-Arg-Cha-Lys-Cha-NH 2 ;
D-Arg-Cha-Lys-NH 2 ;
D-Arg-D-Dmt-NH 2 ;
D-Arg-Dmt-D-Lys-Phe-NH 2 ;
D-Arg-Dmt-Lys-Dmt-Lys-Met-NH 2 ;
D-Arg-Dmt-Lys-Dmt-Lys-Trp-NH 2 ;
D-Arg-Dmt-Lys-D-Phe-NH 2 ;
D-Arg-Dmt-Lys-NH 2 ;
D-Arg-Dmt-Lys-Phe-Lys-Met-NH 2 ;
D-Arg-Dmt-Lys-Phe-Lys-Trp-NH 2 ;
D-Arg-Dmt-Lys-Phe-Met-NH 2 ;
D-Arg-Dmt-Lys-Trp-NH 2 ;
D-Arg-Dmt-NH 2 ;
D-Arg-Dmt-Phe-NH 2 ;
D-Arg-D-Tyr-D-Lys-D-Phe-NH 2 ;
D-Arg-D-Tyr-Lys-Phe-NH 2 ;
D-Arg-D-Tyr-NH 2 ;
D-Arg-Phe-Lys-NH 2 ;
D-Arg-Trp-Lys-NH 2 ;
D-Arg-Trp-Lys-Trp-NH 2 ;
D-Arg-Tyr-D-Lys-Phe-NH 2 ;
D-Arg-Tyr-Lys-D-Phe-NH 2 ;
D-Arg-Tyr-Lys-NH 2 ;
D-Arg-Tyr-Lys-Phe-NH 2 ;
D-Arg-Tyr-NH 2 ;
D-Arg-Tyr-Phe-NH 2 ;
D-Dmt-Arg-NH 2 ;
D-Glu-Asp-Lys-D-Arg-D-His-Phe-Phe-D-Val-Tyr-Arg-Tyr-D-Tyr-Arg-His-Phe-NH 2 ;
D-His-Glu-Lys-Tyr-D-Phe-Arg;
D-His-Lys-Tyr-D-Phe-Glu-D-Asp-D-Asp-D-His-D-Lys-Arg-Trp-NH 2 ;
Dmt-D-Arg-NH 2 ;
Dmt-D-Phe-Arg-Lys-NH 2 ;
Dmt-Lys-D-Phe-NH 2 ;
Dmt-Lys-NH 2 ;
Dmt-Lys-Phe-NH 2 ;
D-Nle-Cha-Ahe-Cha-NH 2 ;
D-Nle-Dmt-Ahe-Phe-NH 2 ;
D-Phe-D-Arg-D-Phe-D-Lys-NH 2 ;
D-Tyr-Arg-NH 2 ;
D-Tyr-Trp-Lys-NH 2 ;
Glu-Arg-D-Lys-Tyr-D-Val-Phe-D-His-Trp-Arg-D-Gly-Tyr-Arg-D-Met-NH 2 ;
Gly-Ala-Lys-Phe-D-Lys-Glu-Arg-Tyr-His-D-Arg-D-Arg-Asp-Tyr-Trp-D-His-Trp-His-D-Lys-Asp;
Gly-D-Phe-Lys-His-D-Arg-Tyr-NH 2 ;
H-D-Arg(NαMe)-Dmt(NMe)-Lys(NαLMe)-Phe(NMe)-NH 2 ;
H-D-Arg-Dmt-Lys(NαMe)-Phe(NMe)-NH 2 ;
H-D-Arg-Dmt-Lys(NαMe)-Phe-NH 2 ;
H-D-Arg-Dmt-Lys-Phe(NMe)-NH 2 ;
H-D-Arg-Dmt-Lys-Phe-Sar-Gly-Cys-NH 2 ;
H-D-Arg-Dmt-LysΨ[CH2-NH]Phe-NH 2 ;
H-D-Arg-Dmt-Ψ[CH2-NH]Lys-Phe-NH 2 ;
H-D-Arg-Dmt-Ψ[CH2-NH]Lys-Ψ[CH2-NH]Phe-NH 2 ;
H-D-Arg-Ψ[CH2-NH]Dmt-Lys-Phe-NH 2 ;
His-Tyr-D-Arg-Trp-Lys-Phe-D-Asp-Ala-Arg-Cys-D-Tyr-His-Phe-D-Lys-Tyr-His-Ser-NH 2 ;
Lys-D-Arg-Tyr-NH 2 ;
Lys-D-Gln-Tyr-Arg-D-Phe-Trp-NH 2 ;
Lys-Dmt-D-Arg-NH 2 ;
Lys-D-Phe-Arg-Dmt-NH 2 ;
Lys-D-Phe-Arg-Tyr-NH 2 ;
Lys-Phe-NH 2 ;
Lys-Trp-D-Tyr-Arg-Asn-Phe-Tyr-D-His-NH 2 ;
Met-Tyr-D-Arg-Phe-Arg-NH 2 ;
Met-Tyr-D-Lys-Phe-Arg;
Phe-Arg-D-His-Asp;
Phe-D-Arg-2′6′-Dmt-Lys-NH 2 ;
Phe-D-Arg-D-Phe-Lys-NH 2 ;
Phe-D-Arg-His;
Phe-D-Arg-Lys-Trp-Tyr-D-Arg-His;
Phe-D-Arg-Phe-D-Lys-NH 2 ;
Phe-D-Arg-Phe-Lys-NH 2 ;
Phe-D-Dmt-Arg-Lys-NH 2 ;
Phe-D-Tyr-Arg-Lys-NH 2 ;
Phe-Lys-Dmt-NH 2 ;
Phe-Phe-D-Tyr-Arg-Glu-Asp-D-Lys-Arg-D-Arg-His-Phe-NH 2 ;
Phe-Tyr-Lys-D-Arg-Trp-His-D-Lys-D-Lys-Glu-Arg-D-Tyr-Thr;
Thr-Gly-Tyr-Arg-D-His-Phe-Trp-D-His-Lys;
Thr-Tyr-Arg-D-Lys-Trp-Tyr-Glu-Asp-D-Lys-D-Arg-His-Phe-D-Tyr-Gly-Val-Ile-D-His-Arg-Tyr-Lys-NH 2 ;
Trp-D-Lys-Tyr-Arg-NH 2 ;
Trp-Lys-Phe-D-Asp-Arg-Tyr-D-His-Lys;
Tyr-Asp-D-Lys-Tyr-Phe-D-Lys-D-Arg-Phe-Pro-D-Tyr-His-Lys;
Tyr-D-Arg-NH 2 ;
Tyr-D-Arg-Phe-Lys-Glu-NH 2 ;
Tyr-D-Arg-Phe-Lys-NH 2 ;
Tyr-D-His-Phe-D-Arg-Asp-Lys-D-Arg-His-Trp-D-His-Phe;
Tyr-D-Phe-Arg-Lys-NH 2 ;
Tyr-His-D-Gly-Met; and
Val-D-Lys-His-Tyr-D-Phe-Ser-Tyr-Arg-NH 2 ,
and further comprising one or more additional active agents selected from the group consisting of cyclosporine, a cardiac drug, an anti-inflammatory, an anti-hypertensive drug, an antibody, an ophthalmic drug, an antioxidant, a metal complexer, and an antihistamine.
29 . The method of claim 28 , wherein the disease or condition comprises a neurological or neurodegenerative disease or condition, ischemia, reperfusion, hypoxia, atherosclerosis, ureteral obstruction, diabetes, complications of diabetes, arthritis, liver damage, insulin resistance, diabetic nephropathy, acute renal injury, chronic renal injury, acute or chronic renal injury due to exposure to nephrotoxic agents and/or radiocontrast dyes, hypertension, metabolic syndrome, an ophthalmic disease or condition such as dry eye, diabetic retinopathy, cataracts, retinitis pigmentosa, glaucoma, macular degeneration, choroidal neovascularization, retinal degeneration, oxygen-induced retinopathy, cardiomyopathy, ischemic heart disease, heart failure, hypertensive cardiomyopathy, vessel occlusion, vessel occlusion injury, myocardial infarction, coronary artery disease, oxidative damage.
30 . The method of claim 28 , wherein the mitochondrial dysfunction comprises mitochondrial permeability transition.
31 . The method of claim 29 , wherein the neurological or neurodegenerative disease or condition comprises Alzheimer's disease, Amyotrophic Lateral Sclerosis (ALS), Parkinson's disease, Huntington's disease or Multiple Sclerosis.
32 . The method of claim 29 , wherein the subject is suffering from ischemia or has an anatomic zone of no-reflow in one or more of cardiovascular tissue, skeletal muscle tissue, cerebral tissue and renal tissue.
33 . The method of claim 32 , wherein the subject is diagnosed as having, suspected of having, or at risk of having atherosclerosis, inflammation, abnormal angiogenesis, abnormal lipid metabolism, abnormal removal of apoptotic cells, ischemia such as cerebral ischemia and myocardial ischemia, ischemia-reperfusion, ureteral obstruction, stroke, Alzheimer's Disease, diabetes, diabetic nephropathy, or obesity.
34 . A method for reducing oxidative damage in a removed organ or tissue, comprising administering to the removed organ or tissue an effective amount of a composition comprising the mitochondria penetrating peptide (MPP) Cha-Arg-Cha-Lys-NH 2 alone or in combination with one or more aromatic-cationic peptides selected from the group consisting of:
2′6′-Dmp-D-Arg-2′6′-Dmt-Lys-NH 2 ;
2′,6′-Dmt-D-Arg-Phe-Lys-NH 2 ;
2′6′-Dmp-D-Arg-Phe-Lys-NH 2 ;
2′6′-Dmt-D-Arg-PheOrn-NH 2 ;
2′6′-Dmt-D-Arg-Phe-Ahp(2-aminoheptanoicacid)-NH 2 ;
2′6′-Dmt-D-Arg-Phe-Lys-NH 2 ;
2′6′-Dmt-D-Cit-PheLys-NH 2 ;
Ala-D-Phe-D-Arg-Tyr-Lys-D-Trp-His-D-Tyr-Gly-Phe;
Arg-D-Dmt-Arg-NH 2 ;
Arg-D-Dmt-Lys-NH 2 ;
Arg-D-Dmt-NH 2 ;
Arg-D-Leu-D-Tyr-Phe-Lys-Glu-D-Lys-Arg-D-Trp-Lys-D-Phe-Tyr-D-Arg-Gly;
Arg-D-Tyr-Arg-NH 2 ;
Arg-D-Tyr-Lys-NH 2 ;
Arg-D-Tyr-NH 2 ;
Asp-Arg-D-Phe-Cys-Phe-D-Arg-D-Lys-Tyr-Arg-D-Tyr-Trp-D-His-Tyr-D-Phe-Lys-Phe;
Asp-D-Trp-Lys-Tyr-D-His-Phe-Arg-D-Gly-Lys-NH 2 ;
D-Arg-2′6′-Dmt-Lys-Phe-NH 2 ;
D-Arg-Arg-Dmt-Phe-NH 2 ;
D-Arg-Arg-Tyr-Phe-NH 2 ;
D-Arg-Cha-Lys-Cha-NH 2 ;
D-Arg-Cha-Lys-NH 2 ;
D-Arg-D-Dmt-NH 2 ;
D-Arg-Dmt-D-Lys-Phe-NH 2 ;
D-Arg-Dmt-Lys-Dmt-Lys-Met-NH 2 ;
D-Arg-Dmt-Lys-Dmt-Lys-Trp-NH 2 ;
D-Arg-Dmt-Lys-D-Phe-NH 2 ;
D-Arg-Dmt-Lys-NH 2 ;
D-Arg-Dmt-Lys-Phe-Lys-Met-NH 2 ;
D-Arg-Dmt-Lys-Phe-Lys-Trp-NH 2 ;
D-Arg-Dmt-Lys-Phe-Met-NH 2 ;
D-Arg-Dmt-Lys-Trp-NH 2 ;
D-Arg-Dmt-NH 2 ;
D-Arg-Dmt-Phe-NH 2 ;
D-Arg-D-Tyr-D-Lys-D-Phe-NH 2 ;
D-Arg-D-Tyr-Lys-Phe-NH 2 ;
D-Arg-D-Tyr-NH 2 ;
D-Arg-Phe-Lys-NH 2 ;
D-Arg-Trp-Lys-NH 2 ;
D-Arg-Trp-Lys-Trp-NH 2 ;
D-Arg-Tyr-D-Lys-Phe-NH 2 ;
D-Arg-Tyr-Lys-D-Phe-NH 2 ;
D-Arg-Tyr-Lys-NH 2 ;
D-Arg-Tyr-Lys-Phe-NH 2 ;
D-Arg-Tyr-NH 2 ;
D-Arg-Tyr-Phe-NH 2 ;
D-Dmt-Arg-NH 2 ;
D-Glu-Asp-Lys-D-Arg-D-His-Phe-Phe-D-Val-Tyr-Arg-Tyr-D-Tyr-Arg-His-Phe-NH 2 ;
D-His-Glu-Lys-Tyr-D-Phe-Arg;
D-His-Lys-Tyr-D-Phe-Glu-D-Asp-D-Asp-D-His-D-Lys-Arg-Trp-NH 2 ;
Dmt-D-Arg-NH 2 ;
Dmt-D-Phe-Arg-Lys-NH 2 ;
Dmt-Lys-D-Phe-NH 2 ;
Dmt-Lys-NH 2 ;
Dmt-Lys-Phe-NH 2 ;
D-Nle-Cha-Ahe-Cha-NH 2 ;
D-Nle-Dmt-Ahe-Phe-NH 2 ;
D-Phe-D-Arg-D-Phe-D-Lys-NH 2 ;
D-Tyr-Arg-NH 2 ;
D-Tyr-Trp-Lys-NH 2 ;
Glu-Arg-D-Lys-Tyr-D-Val-Phe-D-His-Trp-Arg-D-Gly-Tyr-Arg-D-Met-NH 2 ;
Gly-Ala-Lys-Phe-D-Lys-Glu-Arg-Tyr-His-D-Arg-D-Arg-Asp-Tyr-Trp-D-His-Trp-His-D-Lys-Asp;
Gly-D-Phe-Lys-His-D-Arg-Tyr-NH 2 ;
H-D-Arg(NαMe)-Dmt(NMe)-Lys(NαLMe)-Phe(NMe)-NH 2 ;
H-D-Arg-Dmt-Lys(NαMe)-Phe(NMe)-NH 2 ;
H-D-Arg-Dmt-Lys(NαMe)-Phe-NH 2 ;
H-D-Arg-Dmt-Lys-Phe(NMe)-NH 2 ;
H-D-Arg-Dmt-Lys-Phe-Sar-Gly-Cys-NH 2 ;
H-D-Arg-Dmt-LysΨ[CH2-NH]Phe-NH 2 ;
H-D-Arg-Dmt-Ψ[CH2-NH]Lys-Phe-NH 2 ;
H-D-Arg-Dmt-Ψ[CH2-NH]Lys-Ψ[CH2-NH]Phe-NH 2 ;
H-D-Arg-Ψ[CH2-NH]Dmt-Lys-Phe-NH 2 ;
His-Tyr-D-Arg-Trp-Lys-Phe-D-Asp-Ala-Arg-Cys-D-Tyr-His-Phe-D-Lys-Tyr-His-Ser-NH 2 ;
Lys-D-Arg-Tyr-NH 2 ;
Lys-D-Gln-Tyr-Arg-D-Phe-Trp-NH 2 ;
Lys-Dmt-D-Arg-NH 2 ;
Lys-D-Phe-Arg-Dmt-NH 2 ;
Lys-D-Phe-Arg-Tyr-NH 2 ;
Lys-Phe-NH 2 ;
Lys-Trp-D-Tyr-Arg-Asn-Phe-Tyr-D-His-NH 2 ;
Met-Tyr-D-Arg-Phe-Arg-NH 2 ;
Met-Tyr-D-Lys-Phe-Arg;
Phe-Arg-D-His-Asp;
Phe-D-Arg-2′6′-Dmt-Lys-NH 2 ;
Phe-D-Arg-D-Phe-Lys-NH 2 ;
Phe-D-Arg-His;
Phe-D-Arg-Lys-Trp-Tyr-D-Arg-His;
Phe-D-Arg-Phe-D-Lys-NH 2 ;
Phe-D-Arg-Phe-Lys-NH 2 ;
Phe-D-Dmt-Arg-Lys-NH 2 ;
Phe-D-Tyr-Arg-Lys-NH 2 ;
Phe-Lys-Dmt-NH 2 ;
Phe-Phe-D-Tyr-Arg-Glu-Asp-D-Lys-Arg-D-Arg-His-Phe-NH 2 ;
Phe-Tyr-Lys-D-Arg-Trp-His-D-Lys-D-Lys-Glu-Arg-D-Tyr-Thr;
Thr-Gly-Tyr-Arg-D-His-Phe-Trp-D-His-Lys;
Thr-Tyr-Arg-D-Lys-Trp-Tyr-Glu-Asp-D-Lys-D-Arg-His-Phe-D-Tyr-Gly-Val-Ile-D-His-Arg-Tyr-Lys-NH 2 ;
Trp-D-Lys-Tyr-Arg-NH 2 ;
Trp-Lys-Phe-D-Asp-Arg-Tyr-D-His-Lys;
Tyr-Asp-D-Lys-Tyr-Phe-D-Lys-D-Arg-Phe-Pro-D-Tyr-His-Lys;
Tyr-D-Arg-NH 2 ;
Tyr-D-Arg-Phe-Lys-Glu-NH 2 ;
Tyr-D-Arg-Phe-Lys-NH 2 ;
Tyr-D-His-Phe-D-Arg-Asp-Lys-D-Arg-His-Trp-D-His-Phe;
Tyr-D-Phe-Arg-Lys-NH 2 ;
Tyr-His-D-Gly-Met; and
Val-D-Lys-His-Tyr-D-Phe-Ser-Tyr-Arg-NH 2 ,
and further comprising one or more additional active agents selected from the group consisting of cyclosporine, a cardiac drug, an anti-inflammatory, an anti-hypertensive drug, an antibody, an ophthalmic drug, an antioxidant, a metal complexer, and an antihistamine.
35 . The method of claim 34 , wherein the removed organ comprises a heart, lung, pancreas, kidney, liver, or skin.
36 . A method for:
(a) preventing the loss of dopamine-producing neurons in a subject in need thereof,
(b) preventing or treating a burn injury in a subject in need thereof,
(c) treating or preventing mechanical ventilation-induced diaphragm dysfunction in a subject in need thereof,
(d) treating or preventing no reflow following ischemia-reperfusion injury in a subject in need thereof,
(e) preventing norepinephrine uptake in a mammal in need of analgesia,
(f) treating or preventing drug-induced peripheral neuropathy or hyperalgesia in a subject in need thereof,
(f) inhibiting or suppressing pain in a subject in need thereof, or
(h) treating atherosclerotic renal vascular disease (ARVD) in a subject in need thereof,
(i) reducing CD36 expression in a subject in need thereof;
(j) treating or preventing a disease or condition characterized by CD36 elevation in a subject in need thereof; or
(k) reducing oxidative damage associated with a neurodegenerative disease in a subject in need thereof
comprising administering to the subject an effective amount of a composition comprising
the mitochondria penetrating peptide (MPP) Cha-Arg-Cha-Lys-NH 2 alone or in combination with one or more aromatic-cationic peptides selected from the group consisting of:
2′6′-Dmp-D-Arg-2′6′-Dmt-Lys-NH 2 ;
2′,6′-Dmt-D-Arg-Phe-Lys-NH 2 ;
2′6′-Dmp-D-Arg-Phe-Lys-NH 2 ;
2′6′-Dmt-D-Arg-PheOrn-NH 2 ;
2′6′-Dmt-D-Arg-Phe-Ahp(2-aminoheptanoicacid)-NH 2 ;
2′6′-Dmt-D-Arg-Phe-Lys-NH 2 ;
2′6′-Dmt-D-Cit-PheLys-NH 2 ;
Ala-D-Phe-D-Arg-Tyr-Lys-D-Trp-His-D-Tyr-Gly-Phe;
Arg-D-Dmt-Arg-NH 2 ;
Arg-D-Dmt-Lys-NH 2 ;
Arg-D-Dmt-NH 2 ;
Arg-D-Leu-D-Tyr-Phe-Lys-Glu-D-Lys-Arg-D-Trp-Lys-D-Phe-Tyr-D-Arg-Gly;
Arg-D-Tyr-Arg-NH 2 ;
Arg-D-Tyr-Lys-NH 2 ;
Arg-D-Tyr-NH 2 ;
Asp-Arg-D-Phe-Cys-Phe-D-Arg-D-Lys-Tyr-Arg-D-Tyr-Trp-D-His-Tyr-D-Phe-Lys-Phe;
Asp-D-Trp-Lys-Tyr-D-His-Phe-Arg-D-Gly-Lys-NH 2 ;
D-Arg-2′6′-Dmt-Lys-Phe-NH 2 ;
D-Arg-Arg-Dmt-Phe-NH 2 ;
D-Arg-Arg-Tyr-Phe-NH 2 ;
D-Arg-Cha-Lys-Cha-NH 2 ;
D-Arg-Cha-Lys-NH 2 ;
D-Arg-D-Dmt-NH 2 ;
D-Arg-Dmt-D-Lys-Phe-NH 2 ;
D-Arg-Dmt-Lys-Dmt-Lys-Met-NH 2 ;
D-Arg-Dmt-Lys-Dmt-Lys-Trp-NH 2 ;
D-Arg-Dmt-Lys-D-Phe-NH 2 ;
D-Arg-Dmt-Lys-NH 2 ;
D-Arg-Dmt-Lys-Phe-Lys-Met-NH 2 ;
D-Arg-Dmt-Lys-Phe-Lys-Trp-NH 2 ;
D-Arg-Dmt-Lys-Phe-Met-NH 2 ;
D-Arg-Dmt-Lys-Trp-NH 2 ;
D-Arg-Dmt-NH 2 ;
D-Arg-Dmt-Phe-NH 2 ;
D-Arg-D-Tyr-D-Lys-D-Phe-NH 2 ;
D-Arg-D-Tyr-Lys-Phe-NH 2 ;
D-Arg-D-Tyr-NH 2 ;
D-Arg-Phe-Lys-NH 2 ;
D-Arg-Trp-Lys-NH 2 ;
D-Arg-Trp-Lys-Trp-NH 2 ;
D-Arg-Tyr-D-Lys-Phe-NH 2 ;
D-Arg-Tyr-Lys-D-Phe-NH 2 ;
D-Arg-Tyr-Lys-NH 2 ;
D-Arg-Tyr-Lys-Phe-NH 2 ;
D-Arg-Tyr-NH 2 ;
D-Arg-Tyr-Phe-NH 2 ;
D-Dmt-Arg-NH 2 ;
D-Glu-Asp-Lys-D-Arg-D-His-Phe-Phe-D-Val-Tyr-Arg-Tyr-D-Tyr-Arg-His-Phe-NH 2 ;
D-His-Glu-Lys-Tyr-D-Phe-Arg;
D-His-Lys-Tyr-D-Phe-Glu-D-Asp-D-Asp-D-His-D-Lys-Arg-Trp-NH 2 ;
Dmt-D-Arg-NH 2 ;
Dmt-D-Phe-Arg-Lys-NH 2 ;
Dmt-Lys-D-Phe-NH 2 ;
Dmt-Lys-NH 2 ;
Dmt-Lys-Phe-NH 2 ;
D-Nle-Cha-Ahe-Cha-NH 2 ;
D-Nle-Dmt-Ahe-Phe-NH 2 ;
D-Phe-D-Arg-D-Phe-D-Lys-NH 2 ;
D-Tyr-Arg-NH 2 ;
D-Tyr-Trp-Lys-NH 2 ;
Glu-Arg-D-Lys-Tyr-D-Val-Phe-D-His-Trp-Arg-D-Gly-Tyr-Arg-D-Met-NH 2 ;
Gly-Ala-Lys-Phe-D-Lys-Glu-Arg-Tyr-His-D-Arg-D-Arg-Asp-Tyr-Trp-D-His-Trp-His-D-Lys-Asp;
Gly-D-Phe-Lys-His-D-Arg-Tyr-NH 2 ;
H-D-Arg(NαMe)-Dmt(NMe)-Lys(NαLMe)-Phe(NMe)-NH 2 ;
H-D-Arg-Dmt-Lys(NαMe)-Phe(NMe)-NH 2 ;
H-D-Arg-Dmt-Lys(NαMe)-Phe-NH 2 ;
H-D-Arg-Dmt-Lys-Phe(NMe)-NH 2 ;
H-D-Arg-Dmt-Lys-Phe-Sar-Gly-Cys-NH 2 ;
H-D-Arg-Dmt-LysΨ[CH2-NH]Phe-NH 2 ;
H-D-Arg-Dmt-Ψ[CH2-NH]Lys-Phe-NH 2 ;
H-D-Arg-Dmt-Ψ[CH2-NH]Lys-Ψ[CH2-NH]Phe-NH 2 ;
H-D-Arg-Ψ[CH2-NH]Dmt-Lys-Phe-NH 2 ;
His-Tyr-D-Arg-Trp-Lys-Phe-D-Asp-Ala-Arg-Cys-D-Tyr-His-Phe-D-Lys-Tyr-His-Ser-NH 2 ;
Lys-D-Arg-Tyr-NH 2 ;
Lys-D-Gln-Tyr-Arg-D-Phe-Trp-NH 2 ;
Lys-Dmt-D-Arg-NH 2 ;
Lys-D-Phe-Arg-Dmt-NH 2 ;
Lys-D-Phe-Arg-Tyr-NH 2 ;
Lys-Phe-NH 2 ;
Lys-Trp-D-Tyr-Arg-Asn-Phe-Tyr-D-His-NH 2 ;
Met-Tyr-D-Arg-Phe-Arg-NH 2 ;
Met-Tyr-D-Lys-Phe-Arg;
Phe-Arg-D-His-Asp;
Phe-D-Arg-2′6′-Dmt-Lys-NH 2 ;
Phe-D-Arg-D-Phe-Lys-NH 2 ;
Phe-D-Arg-His;
Phe-D-Arg-Lys-Trp-Tyr-D-Arg-His;
Phe-D-Arg-Phe-D-Lys-NH 2 ;
Phe-D-Arg-Phe-Lys-NH 2 ;
Phe-D-Dmt-Arg-Lys-NH 2 ;
Phe-D-Tyr-Arg-Lys-NH 2 ;
Phe-Lys-Dmt-NH 2 ;
Phe-Phe-D-Tyr-Arg-Glu-Asp-D-Lys-Arg-D-Arg-His-Phe-NH 2 ;
Phe-Tyr-Lys-D-Arg-Trp-His-D-Lys-D-Lys-Glu-Arg-D-Tyr-Thr;
Thr-Gly-Tyr-Arg-D-His-Phe-Trp-D-His-Lys;
Thr-Tyr-Arg-D-Lys-Trp-Tyr-Glu-Asp-D-Lys-D-Arg-His-Phe-D-Tyr-Gly-Val-Ile-D-His-Arg-Tyr-Lys-NH 2 ;
Trp-D-Lys-Tyr-Arg-NH 2 ;
Trp-Lys-Phe-D-Asp-Arg-Tyr-D-His-Lys;
Tyr-Asp-D-Lys-Tyr-Phe-D-Lys-D-Arg-Phe-Pro-D-Tyr-His-Lys;
Tyr-D-Arg-NH 2 ;
Tyr-D-Arg-Phe-Lys-Glu-NH 2 ;
Tyr-D-Arg-Phe-Lys-NH 2 ;
Tyr-D-His-Phe-D-Arg-Asp-Lys-D-Arg-His-Trp-D-His-Phe;
Tyr-D-Phe-Arg-Lys-NH 2 ;
Tyr-His-D-Gly-Met; and
Val-D-Lys-His-Tyr-D-Phe-Ser-Tyr-Arg-NH 2 ,
and further comprising one or more additional active agents selected from the group consisting of cyclosporine, a cardiac drug, an anti-inflammatory, an anti-hypertensive drug, an antibody, an ophthalmic drug, an antioxidant, a metal complexer, and an antihistamine.
37 . The method of claim 36 , wherein the subject is diagnosed as having, suspected of having, or at risk of having Parkinson's disease or ALS.
38 . The method of claim 36 , wherein the neurodegenerative disease comprises Alzheimer's disease, Parkinson's disease, or ALS.