APHERESIS, ADMINISTRATION OF AGENT, OR COMBINATION THEREOF

• US 20110033463A1
• Filed: 08/06/2010
• Published: 02/10/2011
• Est. Priority Date: 08/06/2009
• Status: Abandoned Application

• Current Assignee: Medtronic Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Incorporated (Medtronic Plc)
• Inventors: Shafer, Lisa L., Thakker, Deepak R.
• Application Number:
  US12/852,170
• Publication Number:
  US 20110033463A1
• Time in Patent Office: Days
• US Class Current: 424/134.1
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/439 the ring forming part of a bridged ring system, e.g. quinuclidine 8-azabicyclo [3.2.1] octanes A61K31/46
• CPC Class Codes: A61K 31/4406 only substituted in position 3, e.g. zimeldine nicotinic acid A61K31/455
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/55 having seven-membered rings, e.g. azelastine, pentylenetetrazole
• CPC Class Codes: A61K 31/7105 Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
• CPC Class Codes: A61K 38/185 Nerve growth factor [NGF]; Brain derived neurotrophic factor [BDNF]; Ciliary neurotrophic factor [CNTF]; Glial derived neurotrophic factor [GDNF]; Neurotrophins, e.g. NT-3
• CPC Class Codes: A61K 38/1866 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: A61K 38/28 Insulins
• CPC Class Codes: A61K 38/30 Insulin-like growth factors, i.e. somatomedins, e.g. IGF-1, IGF-2 insulin-like growth factor binding protein A61K38/1754
• CPC Class Codes: A61K 38/4813 Exopeptidases (3.4.11. to 3.4.19)
• CPC Class Codes: A61K 38/4886 Metalloendopeptidases (3.4.24), e.g. collagenase
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61M 1/3679 by absorption A61M1/3675 takes precedence
• CPC Class Codes: A61M 2210/0687 Skull, cranium
• CPC Class Codes: A61M 2210/0693 Brain, cerebrum
• CPC Class Codes: A61M 27/006 Cerebrospinal drainage; Accessories therefor, e.g. valves
• CPC Class Codes: A61M 5/14276 specially adapted for implantation
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• 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: C12Y 304/17023 : Angiotensin-converting enzyme 2 (3.4.17.23)
• CPC Class Codes: C12Y 304/24011 : Neprilysin (3.4.24.11), i.e. enkephalinase or neutral endopeptidase 24.11
• CPC Class Codes: C12Y 304/24056 : Insulysin (3.4.24.56)

Abstract

A device is configured to remove a target molecule from a bodily fluid of a subject and to deliver a therapeutic agent to the subject. Such a device may be used for treatment of a disease associated with amyloid beta accumulation in the subject. Agents selected from the group consisting of an ApoE-modulating agent; a RAGE inhibitor; a β-secretase 1 (BACE1) inhibitor; a γ-secretase inhibitor; a muscarinic receptor subtype 1 (M1) agonists; a growth factor; an enzyme capable of degrading amyloid beta; a mitochondrial antioxidant; insulin; and an inhibitor of tumor necrosis factor (TNF) may be administered directly to the central nervous system of a subject for treatment of a disease associated with amyloid beta accumulation.

Claims

1. A method comprising:

withdrawing fluid from a first cerebrospinal fluid compartment of a subject;

passing the withdrawn fluid through a reservoir of a medical device to remove the target molecule from the withdrawn fluid, wherein the reservoir contains a medium comprising a solid support to which an antibody directed to the target molecule is bound and wherein the media is capable of removing the target molecule from the cerebrospinal fluid;

adding a therapeutic agent to the withdrawn fluid with removed target molecule; and

delivering the withdrawn fluid with removed target molecule and added therapeutic agent to a second cerebrospinal fluid compartment of the subject,

wherein the first and second cerebrospinal fluid compartments are the same or different.

2. The method of claim 1, wherein the target molecule is amyloid beta.

3. The method of claim 1, wherein the therapeutic agent is selected from the group consisting of an ApoE-modulating agent;

a RAGE inhibitor;

a β

-secretase 1 (BACE1) inhibitor;

a γ

-secretase inhibitor;

a muscarinic receptor subtype 1 (M1) agonists;

a growth factor;

an enzyme capable of degrading amyloid beta;

a mitochondrial antioxidant;

insulin; and

an inhibitor of tumor necrosis factor (TNF).

4. The method of claim 1, wherein the therapeutic agent is a β

-secretase 1 (BACE1) inhibitor.

5. A method for treating a disease associated with amyloid beta accumulation in a subject in need thereof, comprising:

delivering directly to the central nervous system of the subject a therapeutic agent selected from the group consisting of an ApoE-modulating agent;

a RAGE inhibitor;

a β

-secretase 1 (BACE1) inhibitor;

a γ

-secretase inhibitor;

a muscarinic receptor subtype 1 (M1) agonist;

a growth factor;

an enzyme capable of degrading amyloid beta;

a mitochondrial antioxidant;

insulin; and

an inhibitor of tumor necrosis factor (TNF).

6. The method of claim 5, further comprising delivering an anti-amyloid beta antibody to the subject.

7. The method of claim 5, wherein the therapeutic agent is a liver X receptor (LXR) agonist.

8. The method of claim 5, wherein the therapeutic agent is the RAGE inhibitor, PF-04494700.

9. The method of claim 5, wherein the therapeutic agent is a γ

-secretase inhibitor selected from the group consisting of r-flurbiprofen, MCP-7869, LY-450139, LY411575, and MK0752.

10. The method of claim 5, wherein the therapeutic agent is an M1 agonist selected from the group consisting of cevimeline, talsaclidine, sabcomeline and milameline, xanomeline, and 5-(3-ethyl-1,2,4-oxadiazol-5-yl)-1,4,5,6-tetrahydropyrimmidine (CDD-0102).

11. The method of claim 5, wherein, wherein the therapeutic agent is a growth factor selected from the group consisting of VEGF, BDNF, NGF, and IGF-1.

12. The method of claim 5, wherein the therapeutic agent is an enzyme capable of degrading amyloid beta selected from the group consisting of neprilysin, insulin-degrading enzyme (IDE), angiotensin-converting enzyme (ACE), and insulysin.

13. The method of claim 5, wherein the therapeutic agent is the microtubule stabilizing agent, NAP (AL-108).

14. The method of claim 5, wherein the therapeutic agent is a β

-secretase 1 (BACE1) inhibitor.

15. The method of claim 5, wherein the therapeutic agent is insulin.

16. The method of claim 5, wherein the therapeutic agent is an inhibitor of tumor necrosis factor.

17. The method of claim 5, wherein the therapeutic agent is administered to cerebrospinal fluid of the subject.

18. The method of claim 5, wherein the therapeutic agent is administered intraparenchymally.

19. The method of claim 5, wherein the therapeutic agent is administered to a hippocampus of the subject.