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Method and vaccine comprising copolymer 1 for treatment of psychiatric disorders

a psychiatric disorder and copolymer technology, applied in the field of copolymer 1 and related peptides, polypeptides and t cells, can solve the problems of poor long-term outcome, chronic morbidity, and failure of studies over the last 60 years aimed at identifying schizophrenia as an autoimmune disease, so as to improve cognitive function and lessen behavioral abnormalities

Inactive Publication Date: 2011-05-19
EISENBACH SCHWARTZ MICHAL +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0014]It has now been found, in accordance with the present invention, that vaccination with Copolymer 1 can lessen behavioral abnormalities and improve cognitive function in mice suffering from dopamine imbalance induced by MK-801 or amphetamine.

Problems solved by technology

Whereas the positive symptoms usually respond well to dopamine-receptor antagonists (which however have significant and devastating side effects such as induction of Parkinson's disease), the negative symptoms and cognitive deficits typically persist, resulting in chronic morbidity and poor long-term outcome (Rummel et al., 2003).
However, studies over the last 60 years aimed at identifying schizophrenia as an autoimmune disease have so far been unsuccessful (Amital and Shoenfeld, 1993).

Method used

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  • Method and vaccine comprising copolymer 1 for treatment of psychiatric disorders
  • Method and vaccine comprising copolymer 1 for treatment of psychiatric disorders
  • Method and vaccine comprising copolymer 1 for treatment of psychiatric disorders

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0096]Vaccination with Cop-1 has an Anti-Psychotic Effect and Protects Against Sensorimotor Dysfunction induced by Psychotomimetic Agents

[0097]Dizocilpine maleate ((+)MK-801, an antagonist of the N-methyl-D-aspartate (NMDA) receptor channel) and AMPH act as psychotomimetic agents, inducing—via neurotransmitter imbalance—psychotic symptoms in healthy individuals and exacerbating psychotic symptoms in schizophrenic patients (Lahti et al., 2001). We therefore used these two compounds in an animal model to induce psychotic behavior that simulates behavioral and cellular abnormalities associated with schizophrenia (Tenn et al., 2003).

[0098]The neurotransmitter imbalance induced by MK-801 or AMPH also causes sensorimotor dysfunction, another characteristic feature of patients with schizophrenia. Because (as shown below) T cell-based therapy counteracted the effect of these drugs on cognition, we assumed that other functions impaired by these drugs would be similarly affected. Sensorimotor...

example 2

Cognitive Functions are Impaired in the Absence of T Cells

[0100]To establish whether learning and memory processes are dependent on the integrity of the immune system, we compared the spatial learning / memory of wild-type and SCID BALB / c / OLA mice, by using the MWM, a hippocampal-dependent visuo-spatial learning / memory task. The SCID mice manifested significant impairment of spatial memory compared with their wild-type counterparts (FIGS. 2a-2c). During the acquisition (FIG. 2a), extinction (FIG. 2b), and reversal (FIG. 2c) phases of the MWM task, mice devoid of adaptive immunity showed significantly increased latency in finding the hidden platform compared with wild-type mice (FIGS. 2a-2c). Unlike the wild-type, the immune-deficient (SCID) mice failed to recall data from the previous day's training trial (FIGS. 2a, 2c). Moreover, the SCID mice started out at a lower level of performance than the wild-type, indicating that their general skills in carrying out the task were impaired, a...

example 3

Cop-1 Vaccination is Protective Against Cognitive Impairment Induced by Psychotomimetic Agents

[0102]The above results encouraged us to examine the possibility that, in mice with impaired cognitive functions caused for example by neurotransmitter imbalance, boosting of the relevant T cells (e.g., by T cell-based vaccination) might have a therapeutic effect.

[0103]As mentioned above, MK-801 and AMPH induce in humans psychotic symptoms. In mice, such symptoms evidently simulate the cognitive impairment and behavioral abnormalities associated with schizophrenia (Tenn et al., 2003). A number of authors have reported an MK-801-induced deficit in acquisition of spatial memory (Whishaw et al., 1989; Ahlander et al., 1999) and nonspatial memory tasks (Griesbach et al., 1998).

[0104]To examine whether T cell-based vaccination can overcome behavioral abnormalities and cognitive impairment resulting from neurotransmitter imbalance, we immunized mice with Cop-1. This synthetic antigen apparently a...

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Abstract

Copolymer 1, a Copolymer 1-related peptide, a Copolymer 1-related polypeptide, and T cells activated therewith are useful in methods and compositions for treatment of psychiatric disorders, diseases and conditions.

Description

FIELD OF THE INVENTION[0001]The present invention relates to compositions and methods for treatment of psychiatric disorders and, in particular, to Copolymer 1 and related peptides and polypeptides and T cells treated therewith for use in such compositions and methods.[0002]Abbreviations: AMPH: D-amphetamine sulfate; ASR: acoustic startle response; BDNF: brain-derived neurotrophic factor; CBC: cut-off behavioral criteria; CFA: complete Freund's adjuvant; CNS: central nervous system; COP-1: copolymer 1; EPM: Elevated plus-maze; MBP: myelin basic protein; MK-801: (+)dizocilpine maleate; MWM: Morris water maze; PNS: peripheral nervous system; PPI: prepulse inhibition; PTSD: post-traumatic stress disorder; SCID:severe combined immune deficiency; Teff: effector T cells; Treg: regulatory T cells; WT: wild-type.BACKGROUND OF THE INVENTION[0003]Mental disorders are now known to be characterized not only by behavioral abnormalities but also by somatic manifestations. In a number of psychiatr...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K39/00A61K38/07A61K38/02A61K35/12A61P25/18A61P37/04A61K31/00A61K45/00A61P1/16A61P11/06A61P31/12A61P31/14A61P35/00A61P37/06A61P37/08C07K14/705C07K16/28C12N1/15C12N1/19C12N1/21C12N15/09C12P21/02C12Q1/02C12Q1/68G01N33/15G01N33/53G01N33/564G01N33/566
CPCA61K31/00C07K14/705G01N2500/00G01N33/566G01N33/564A61P1/16A61P11/06A61P25/18A61P31/12A61P31/14A61P35/00A61P37/04A61P37/06A61P37/08C07K14/435C07K16/00C12N15/11C12N15/63
Inventor EISENBACH-SCHWARTZ, MICHALKIPNIS, JONATHAN
Owner EISENBACH SCHWARTZ MICHAL
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