Delivery of polynucleotide agents to the central nervous system

• US 20060216317A1
• Filed: 12/29/2005
• Published: 09/28/2006
• Est. Priority Date: 04/20/2001
• Status: Abandoned Application

• Current Assignee: Christoph Reinhard, William H. Frey, II
• Original Assignee: Christoph Reinhard, William H. Frey, II
• Inventors: Reinhard, Christoph, Frey, William H. II
• Application Number:
  US11/323,644
• Publication Number:
  US 20060216317A1
• Time in Patent Office: Days
• US Class Current: 424/400
• CPC Class Codes: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 21/02 Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/08 Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/18 Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 25/30 for treating abuse or dependence
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/315 Phosphorothioates
• CPC Class Codes: C12N 2310/317 with an inverted bond, e.g. a cap structure
• CPC Class Codes: C12N 2310/321 2'-O-R Modification
• CPC Class Codes: C12N 2310/335 Modified T or U
• CPC Class Codes: C12N 2310/341 : Gapmers, i.e. of the type ===---===
• CPC Class Codes: C12N 2310/346 : having a combination of backbone and sugar modifications
• CPC Class Codes: C12N 2310/3521 : Methyl

Abstract

The present invention provides a method for delivering polynucleotide agents, particularly oligonucleotides, to the CNS of a mammal by way of a neural pathway originating in the nasal cavity or through a neural pathway originating in an extranasal tissue that is innervated by the trigeminal nerve.

Claims

1-23. -23. (canceled)

24. A method for delivering a polynucleotide agent to the central nervous system of a mammal, comprising:

contacting an olfactory region of a nasal cavity or a tissue innervated by a trigeminal nerve with a composition comprising the agent whereby the agent is delivered to the tissues and cells of the central nervous system.

25. The method of claim 24, wherein the olfactory region comprises a nerve pathway, an epithelial pathway, a lymphatic channel, a perivascular channel, or a combination thereof.

26. The method of claim 24, wherein the composition comprising the polynucleotide agent is contacted with the mammal'"'"'s olfactory region by administering the composition into an upper third of the nasal cavity.

27. The method of claim 24, wherein the tissue innervated by the trigeminal nerve is an intranasal tissue or an extranasal tissue selected from the group consisting of an oral tissue, a dermal tissue, or a conjunctiva.

28. The method of claim 24, wherein contacting the composition with the oral tissue comprises sublingual administration.

29. The method of claim 24, wherein the polynucleotide agent is delivered to a spinal cord, a brain stem, a mid-brain, a cerebellum, an olfactory bulb, a cortical structure, a subcortical structure, or any combination thereof.

30. The method of claim 24, wherein the polynucleotide agent is selected from the group consisting of a polynucleotide, a polynucleotide analogue, a polynucleotide mimic, and a plasmid operatively coding for a biologically active peptide or protein.

31. A method of inhibiting translation of a mRNA that encodes a target protein that contributes to the pathology of a central nervous system disorder of a mammal, comprising:

providing a composition comprising at least one antisense agent that is complementary to a region of the mRNA; and

contacting the composition with an olfactory region of the mammal'"'"'s nasal cavity or with a tissue that is innervated by the trigeminal nerve, whereby the antisense agent is delivered to a cell of the central nervous system that comprises the mRNA, wherein the antisense agent hybridizes to the target mRNA and inhibits translation.

32. The method of claim 31, wherein the antisense agent is selected from the group consisting of an oligonucleotide, a chemically modified oligonucleotide, and a peptide nucleic acid molecule.

33. The method of claim 31, wherein the composition comprising the antisense molecule is contacted with the mammal'"'"'s olfactory region by administering the composition into an upper third of the nasal cavity.

34. The method of claim 31, wherein the target protein is selected from the group consisting of:

an insulin-like growth factor receptor I (IGF-IR), insulin-like growth factor-I (IGF-I), insulin-like growth factor II (IGF-II), an insulin-like growth factor-II (IGF-II) receptor, a Beta-Amyloid Precursor Protein, and an opiate receptor.

35. The method of claim 31, wherein the tissue innervated by the trigeminal nerve is an intranasal tissue or an extranasal tissue selected from the group consisting of an oral tissue, a dermal tissue, or a conjunctiva.

36. The method of claim 31, wherein contacting the composition with the oral tissue comprises sublingual administration.