Compositions and Methods for Treating Dopamine Disorders
Compositions comprising clathrin nanoparticles and methods for treating dopamine-associated addictions, disorders, and neurodegenerative diseases using the same.
1 . A composition comprising:
(i) a DAT targeting agent; and (ii) a neurotrophin, wherein the DAT targeting agent and neurotrophin are linked to a clathrin nanoparticle.
2 . The composition of claim 1 , wherein the clathrin nanoparticle comprises a clathrin cage.
3 . The composition of claim 1 , wherein the clathrin nanoparticle consists of a clathrin triskelion consisting of 1 to 3 clathrin heavy chains (CHCs) and 0-3 clathrin light chains (CLCs).
4 . The composition of claim 1 , wherein the clathrin nanoparticle comprises a complex consisting of 1 to 3 clathrin heavy chains (CHCs), optionally wherein one or more of the CHCs is further linked to one human clathrin light chain.
5 . The composition of claim 1 , wherein the DAT targeting agent comprises a dopamine re-uptake inhibitor (DRI) or an anti-DAT antibody.
6 . The composition of claim 5 , wherein the dopamine reuptake inhibitor (DRI) is selected from the group consisting of -Hydroxy-1-methyl-4-(4-methylphenyl)-3-piperidyl 4-methylphenyl ketone, Altropane (O-587), Amfonelic acid (WIN 25978), Amineptine, BTCP (GK-13), 3C-PEP, DBL-583, Difluoropine (O-620), GBR-12783, GBR-12935, GBR-13069, GBR-13098, GYKI-52895, Iometopane (β-CIT, RTI-55), Methylphenidate, Ethylphenidate, Modafinil, Armodafinil, RTI-229, Vanoxerine (GBR-12909), drafinil, Amantadine, Benztropine, Bupropion, Fluorenol, Ketamine, Medifoxamine, Metaphit, Rimcazole, Sertraline, St. John's Wort, Venlafaxine, Chaenomeles speciose, 3-Methoxyphencyclidine, 4-Methoxyphencyclidine, and Oroxylin A.
7 . The composition of claim 1 , wherein the neurotrophin comprises BDNF, NGF, NT-3, NT-4, NT-6, GDNF, NTN, PSPN, ARTN, CNTF, or LIF.
8 . The composition of claim 1 , wherein the DAT targeting agent and/or the neurotrophin is linked to the clathrin nanoparticle by conjugation.
9 . The composition of claim 8 , wherein the DAT targeting agent is conjugated to the clathrin nanoparticles via PEG
10 . The composition of claim 8 , wherein the neurotrophin is conjugated to the clathrin nanoparticles, optionally to a CHC, via PEG
11 . The method of composition of claim 4 , wherein the DAT targeting agent and the neurotrophin are linked to the same CHC, or to different CHCs.
12 . The composition of claim 4 , wherein at least one clathrin heavy chain is linked to 1 to 5 molecules of the DAT targeting agent and/or 1 to 5 molecules of the neurotrophin.
13 . The composition of claim 4 , wherein a clathrin heavy chain is linked to 1 to 5 molecules of the DAT targeting agent and 1 to 5 molecules of the neurotrophin.
14 . The composition of claim 4 , wherein at least one CHC is linked to one molecule of BDNF and four molecules of a DRI, or one molecule of BDNF and three molecules of an anti-DAT antibody.
15 . The method of claim 21 , wherein the dopamine disorder is a neurodegenerative disease associated with loss of dopaminergic neurons.
16 . The method of claim 15 , wherein the neurodegenerative disease associated with loss of dopaminergic neurons is Parkinson's disease, Huntington's disease, Alzheimer's disease, or ALS.
17 . The method of claim 21 , wherein the dopamine disorder is ADHD, depression, or schizophrenia.
18 . The method of claim 21 , wherein the dopamine disorder is a dopamine-driven addiction.
19 . (canceled)
20 . The method of claim 21 , wherein the composition is delivered intranasally or intravenously.
21 . A method for treating a human subject having or at risk for developing a dopamine disorder comprising administering to the human subject a therapeutically effective amount of the composition of claim 1 .