Eye-Drop Vaccine Containing Copolymer 1 for Therapeutic Immunization

a technology of eyedrops and copolymers, applied in the field of immunology, can solve the problems of no benefit to retinal ganglion cells suffering from iop elevated insult, damage to the nervous system, and no publication discloses immunizations

Inactive Publication Date: 2007-10-25
YEDA RES & DEV CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0018] It has now been found, in accordance with the present invention, that Copolymer 1, when administered as an eye-drop vaccine, evokes a systemic T cell-dependent immune response needed for neuroprotection in the CNS or PNS, as exemplified by protection of retinal ganglion cells (RGCs) against death induced by acute or chronic intraocular pressure (IOP) elevation.
[0022] In a further aspect, the present invention provides a method of therapeutic immunization for treating neuronal degeneration caused by an injury, disease, disorder or condition in the central nervous system (CNS) or peripheral nervous system (PNS), for preventing or inhibiting neuronal secondary degeneration which may otherwise follow a primary injury in the CNS, for promoting nerve regeneration in the CNS or in the PNS after an injury, disease, disorder or condition or for protecting CNS and PNS cells from glutamate toxicity, which comprises immunizing an individual in need with an eye-drop vaccine comprising an active agent selected from the group consisting of Copolymer 1, a Copolymer 1-related peptide, and a Copolymer 1-related polypeptide, in an amount effective to treat, prevent or inhibit said neuronal degeneration caused by said injury, disease, disorder or condition in the individual.

Problems solved by technology

Damage to the nervous system may result from a traumatic injury, such as penetrating trauma or blunt trauma, or a disease, disorder or condition, including but not limited to Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, diabetic neuropathy, glaucoma, senile dementia, and ischemia.
In contrast, the use of peptides derived from compounds residing in the myelin associated with the optic nerve led to no benefit to the retinal ganglion cells suffering from IOP elevated insult.
None of these publications discloses immunization by administration of eye-drops containing Cop 1.

Method used

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  • Eye-Drop Vaccine Containing Copolymer 1 for Therapeutic Immunization
  • Eye-Drop Vaccine Containing Copolymer 1 for Therapeutic Immunization

Examples

Experimental program
Comparison scheme
Effect test

example 1

Cop-1 Vaccination Protects RGCs From IOP-Induced Death When Given Without Vehicle

[0080] Previous studies have shown that Cop 1 emulsified in an adjuvant protects against IOP-induced RGC death. Here we examined whether the effect is long-lasting in a chronic model.

[0081] Animals were subjected to unilateral elevation of IOP and immunized on the day of laser treatment (to induce IOP elevation). Rats were subjected to chronic elevation of IOP on the day of the first laser irradiation. Animals were divided into 4 groups: two groups received Cop-1 emulsified in CFA and two groups received PBS in CFA. From one group of Cop-1-treated animals retinas were excised 3 weeks later and the second group received Cop-1 2, 6 and 9 weeks latter. From this group, retinas were excised 12 weeks after the first laser irradiation. Of the two PBS-CFA-treated groups, one was analyzed for RGC survival 3 weeks after the first laser irradiation, and one received additional injection of PBS-CFA at 2, 6 and 9...

example 2

Cop-1 Immunization Without Adjuvant

[0082] Since Cop-1 is a high molecular weight compound with multiple epitopes, we considered the possibility that it might be immunogenic even without adjuvant.

[0083] In a first experiment, rats were subjected to IOP elevation and received subcutaneous injection of different dosages of adjuvant-free Cop-1 at various dosages (100, 250, 500 and 1000 μg) on the first day of laser treatment; control animals received PBS. The results are depicted in FIG. 2A and show that the optimal effect could be achieved with 500 μg of Cop-1 injected subcutaneously to the rat; higher dosage or lower were less effective. The group treated with 500 μg showed the highest effect: 26.6±10% of RGC death as compared to 44±6% of RGC death in the group treated with 100 μg and 50.5±8% of RGC death in the group treated with 250 μg. In all groups 4-6 animals were included.

[0084] In another experiment, we also examined the timing and the frequency and found that injection on d...

example 3

Cop-1 Effect is T-Cell Dependent

[0086] To verify that the effect of Cop-1 is indeed immune-mediated and does not act as a local drug, we administered Cop-1 to animals deprived of T cells in which IOP was elevated.

[0087] In a first experiment, normal adult rats and adult rats deprived of T cells (as a result of thymectomy at birth) were subjected to elevated IOP. Immediately after IOP elevation, animals received Cop-1, a single injection, or PBS, or daily brimonidine. Three weeks later retinae were excised and RGCs were counted. A lower percentage of RGCs died in non-thymectomized animals than in thymectomized animals following IOP elevation (34±3 vs. 50.2±3, p<0.001, n=6 and 5, respectively). As shown in FIGS. 3A and 3B, in the thymectomized animals treated with the α2-adrenoreceptor agonist glaucoma drug brimonidine, the loss of RGCs was lower than in the non-treated thymectomized or in the Cop-1-treated thymectomized rats [38±7 (n=6) vs. 55±5.2 (n=5); p=0.001]. The effect of bri...

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Abstract

The invention provides an eye-drop vaccine for therapeutic immunization of a mammal comprising Copolymer 1, a Copolymer 1-related peptide, or a Copolymer 1-related polypeptide, for treating neuronal degeneration caused by an injury or disease, disorder or condition in the central nervous system (CNS) or peripheral nervous system (PNS), for preventing or inhibiting neuronal secondary degeneration which may otherwise follow primary injury in the CNS, for promoting nerve regeneration in the CNS or in the PNS after an injury, disease, disorder or condition or for protecting CNS and PNS cells from glutamate toxicity.

Description

FIELD OF THE INVENTION [0001] The present invention is in the field of Immunology and relates to an eye-drop vaccine comprising a random copolymer, in particular Copolymer 1, a Copolymer 1-related peptide, or a Copolymer 1-related polypeptide, as the active agent, and to a method of therapeutic immunization of a mammal, in particular for neuroprotection in the central nervous system (CNS) or in the peripheral nervous system (PNS) after an injury, disease, disorder or condition or for protecting CNS and PNS cells from glutamate toxicity. [0002] Abbreviations: BSA: bovine serum albumin; CFA: complete Freund's adjuvant; CNS: central nervous system; Cop 1: Copolymer 1, glatiramer acetate; FCS: fetal calf serum; IFA: incomplete Freund's adjuvant; IOP: intraocular pressure; MBP: myelin basic protein; NS: nervous system; PBS: phosphate-buffered saline; PNS: peripheral nervous system; RGC: retinal ganglion cells. BACKGROUND OF THE INVENTION [0003] The nervous system comprises the central an...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/7088A61K38/20A61K38/21A61P25/28A61KA61K6/00A61K9/00A61K38/00A61K39/00A61K39/39A61K47/00A61P25/00A61P27/06
CPCA61K9/0048A61K38/2013A61K38/193A61K39/0008A61K38/217A61K38/208A61K31/7088A61K38/02A61K2300/00A61P1/14A61P1/16A61P3/10A61P5/06A61P9/10A61P11/00A61P25/00A61P25/02A61P25/08A61P25/14A61P25/16A61P25/18A61P25/22A61P25/28A61P25/30A61P25/36A61P27/02A61P27/06A61P37/02A61P37/06A61P39/02
Inventor EISENBACH-SCHWARTZ, MICHALBAKALASH, SHARONFULGA, VALENTIN
Owner YEDA RES & DEV CO LTD
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