Modulation of Synaptic Maintenance

• US 20120195880A1
• Filed: 12/14/2011
• Published: 08/02/2012
• 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.
• Granted Patent: US 9,149,444 B2
• Time in Patent Office: Days
• US Class Current: 424/130.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 31/727 Heparin; Heparan
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• 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: 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: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• 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 33/5032 on intercellular interactions
• 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 Alzheimer'"'"'s disease.

Claims

1. A method of inhibiting synapse loss comprising the step of:

administering a therapeutic amount of a complement inhibitor to a patient suffering from adverse synapse loss.

2. The method according to claim 1, wherein said patient has suffered synapse loss as a result of a neurodegenerative disorder.

3. The method of claim 2, wherein said degenerative disorder is a central nervous system disorder.

4. The method according to claim 2, wherein said degenerative disorder is a peripheral nervous system disorder.

5. The method of claim 3, wherein said neurodegenerative disorder is Alzheimer'"'"'s disease.

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

7. The method according to claim 1, wherein synapse loss is inhibited in said patient.

8. The method according to claim 1, wherein said agent upregulates expression of a complement inhibitor in neural cells.

9. The method of claim 1, wherein said agent inhibits expression of C1q in neural cells.

10. The method of claim 1, wherein said agent inhibits complement activation.

11. The method of claim 1, wherein said agent binds to C1q.

12. A method of screening a candidate agent for activity in inhibiting synapse loss, the method comprising:

contacting a neural cell culture with a candidate agent, wherein said agent is an antagonist or agonist of complement;

quantitating the formation of synapses in culture.

13. The method of claim 12, wherein said neural cell culture is a retinal ganglion cell culture.

14. The method of claim 12, wherein said further comprises an astrocyte feeder layer.