Modulation of Synaptic Maintenance

• US 20120328601A1
• Filed: 08/15/2012
• Published: 12/27/2012
• Est. Priority Date: 12/09/2005
• Status: Active Grant

• Current Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Original Assignee: Board of Trustees of the Leland Stanford Junior University (Stanford Management Co.)
• Inventors: Barres, Ben A., Stevens, Beth A., Stephan, Alexander H.
• Granted Patent: US 9,480,658 B2
• Time in Patent Office: Days
• US Class Current: 424/130.1
• 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 31/00 Medicinal preparations containing organic active ingredients
• CPC Class Codes: A61K 31/7088 Compounds having three or more nucleosides or nucleotides
• CPC Class Codes: A61K 31/727 Heparin; Heparan
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 38/1774 Immunoglobulin superfamily (e.g. CD2, CD4, CD8, ICAM molecules, B7 molecules, Fc-receptors, MHC-molecules)
• CPC Class Codes: A61K 38/482 Serine endopeptidases (3.4.21)
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2320/30 Special therapeutic applications
• CPC Class Codes: G01N 2333/4716 Complement proteins, e.g. anaphylatoxin, C3a, C5a
• CPC Class Codes: G01N 2500/04 Screening involving studying the effect of compounds C directly on molecule A (e.g. C are potential ligands for a receptor A, or potential substrates for an enzyme A)
• CPC Class Codes: G01N 2800/28 Neurological disorders
• CPC Class Codes: G01N 2800/2821 Alzheimer
• CPC Class Codes: G01N 33/5058 Neurological cells
• CPC Class Codes: G01N 33/564 for pre-existing immune complex or autoimmune disease , i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
• CPC Class Codes: G01N 33/6872 : Intracellular protein regulatory factors and their receptors, e.g. including ion channels
• CPC Class Codes: G01N 33/6896 : Neurological disorders, e.g. Alzheimer's disease

Abstract

C1q is shown to be expressed in neurons, where it acts as a signal for synapse elimination. Methods are provided for protecting or treating an individual suffering from adverse effects of synapse loss. These findings have broad implications for a variety of clinical conditions, including treating and preventing neurodegenerative diseases such as Alzheimer'"'"'s disease.

Claims

1. A method of treating aging-associated cognitive decline in a patient, comprising:

administering a therapeutic amount of a complement inhibitor to a patient suffering from cognitive decline.

2. The method according to claim 1, wherein the aging-associated cognitive decline is associated with natural aging.

3. The method according to claim 1, wherein the aging-associated cognitive decline is associated with a neurodegenerative disorder.

4. The method according to claim 3, wherein the neurodegenerative disorder is Alzheimer'"'"'s disease.

5. The method according to claim 1, wherein the complement inhibitor inhibits complement activation.

6. The method according to claim 1, wherein the complement inhibitor inhibits the activity of the C1 complex.

7. The method according to claim 6, wherein the complement inhibitor inhibits C1s.

8. The method according to claim 1, further comprising administration of neural progenitors, or a neurogenesis enhancer.

9. The method according to claim 1, wherein cognitive decline is inhibited in the patient.

10. A method of screening a candidate agent for activity in inhibiting cognitive decline, the method comprising:

contacting a cell culture with a candidate agent; and

comparing the level of complement activity in the cell culture to the level of complement activity in a cell culture not contacted with the candidate agent,

wherein a decrease in the amount of complement activity in the contacted cell culture indicates that the candidate agent will inhibit cognitive decline.

11. The method according to claim 10, wherein the cell culture is a neural cell culture.

12. The method according to claim 11, wherein said further comprises an astrocyte feeder layer.

13. The method according to claim 11, wherein the neural cell culture is a retinal ganglion cell culture.

14. The method according to claim 11, further comprising quantifying synapse loss.