KR20190063950A - Composition comprising MECP2 protein or polynucleotide encoding the MECP2 for prevention and treatment of of neurodegenerative disease - Google Patents

Abstract

The present invention relates to a composition for preventing or treating degenerative brain diseases containing an MECP2 protein, a polynucleotide encoding the same, or a recombinant virus comprising the same as an active component for treating degenerative brain diseases. The composition can be usefully used for treating degenerative brain diseases caused by amyloid β, particularly, Alzheimer′s syndrome and for relieving or alleviating cognitive dysfunction and sociality deficiency symptoms caused by Alzheimer′s syndrome.

Description

A composition for preventing or treating a degenerative brain disease comprising a MECP2 protein or a polynucleotide encoding the MECP2 protein or a polynucleotide encoding the MECP2 protein or polynucleotide encoding the same,

The present invention relates to a composition for the prevention or treatment of degenerative brain diseases comprising an MECP2 protein, a polynucleotide encoding the same, or a recombinant virus comprising the same as an active ingredient. More particularly, the present invention relates to a composition for preventing or treating degenerative brain diseases, To a composition for the prevention or treatment of degenerative brain diseases which can be used for the treatment of degenerative brain diseases or for the amelioration of symptoms by directly administering a substance which can be used for treating degenerative brain diseases or by delivering viruses expressing them.

As we enter the aging society, interest in aging-related diseases is increasing. Alzheimer's Dementia (50%), which is known to be caused by vascular dementia (20-30%) caused by stenosis or occlusion of the blood vessels and amyloid beta protein accumulated in the brain, is a typical degenerative brain disease among cerebral diseases such as stroke and Alzheimer's. ), And mixed dementia (15-20%) caused by a combination of these two causes.

To date, extensive and diverse studies have been conducted on the etiology and treatment of dementia. However, the cause of dementia remains unknown and the development of effective therapies is still insufficient. Although tacrine, rivastigmine, galantamine, donepezil and memantine have been approved by the FDA for the treatment of Alzheimer's dementia, currently used dementia treatments can be treated It is only a temporary relief of progression or symptom, not the drug that makes it more effective. Moreover, as the progression of neuronal cell death progresses, the effect of drug decreases, and severe dementia is ineffective. In addition, most of these drugs have side effects such as hepatotoxicity and damaging the mucous membranes of digestive organs, which are anti-inflammatory drugs, and they are limited to the treatment rather than the ultimate cause treatment.

Currently, several pharmaceutical companies are spurring R & D for the development of dementia-related drugs, but the economic and social effects of new drug development are large, but their development cost is too high to develop easily.

Accordingly, the inventors of the present invention completed the present invention by confirming that the animal model of Alzheimer's disease shows an improvement effect of cognitive ability and a sociability improvement while studying a therapeutic agent having no dysfunction of the body and an effect of treating dementia.

Patent Document 1: Korean Patent Laid-Open Publication No. 10-2011-0066595

Disclosure of the Invention The present invention has been conceived to solve the above problems, and an object of the present invention is to provide a pharmaceutical composition for preventing or treating degenerative brain diseases, which comprises the MECP2 protein of SEQ ID NO: 1 and a polynucleotide encoding the MECP2 protein as an active ingredient .

Another object of the present invention is to provide a method for preventing or treating degenerative brain diseases comprising a recombinant vector comprising the MECP2 protein of SEQ ID NO: 1 and a polynucleotide encoding the same, a recombinant cell comprising the recombinant vector, And to provide a pharmaceutical composition.

It is still another object of the present invention to provide a composition for diagnosing degenerative brain diseases comprising a primer, a probe or an antibody for detecting MECP2 protein and a polynucleotide encoding the MECP2 protein.

It is another object of the present invention to provide a gene detection method for providing degenerative brain disease diagnosis information and a candidate substance screening method for a degenerative brain disease therapeutic agent.

In order to achieve the above object, the present invention provides a pharmaceutical composition for preventing or treating a degenerative brain disease comprising, as an active ingredient, MECP2 (methyl CpG binding protein 2) protein of SEQ ID NO: 1 or a polynucleotide encoding the same.

The degenerative brain disease is selected from the group consisting of Parkinson's disease, Alzheimer's dementia (senile dementia), stroke, Lou Gehrig's disease, Pick's disease, Creutzfeldt Jakob disease, Huntington's disease, progressive supranuclear palsy, spinal cord cerebellar atrophy, cerebellar atrophy, Loss of interest may be selected from the group consisting of:

The present invention also provides a recombinant vector expressing a gene encoding MECP2 (methyl CpG binding protein 2) of SEQ ID NO: 1, a recombinant cell comprising the recombinant vector, or a mixture thereof as an active ingredient Or a pharmaceutically acceptable salt thereof.

The degenerative brain disease is selected from the group consisting of Parkinson's disease, Alzheimer's dementia (senile dementia), stroke, Lou Gehrig's disease, Pick's disease, Creutzfeldt Jakob disease, Huntington's disease, progressive supranuclear palsy, spinal cord cerebellar atrophy, cerebellar atrophy, Loss of interest may be selected from the group consisting of:

The degenerative brain disease may be Alzheimer ' s dementia due to accumulation of amyloid beta.

Another object of the present invention is to provide a composition for diagnosing degenerative brain diseases comprising a primer, a probe or an antibody for detecting MECP2 protein and a polynucleotide encoding the MECP2 protein.

According to another aspect of the present invention, there is provided a method for detecting an MECP2 protein comprising the steps of: a) measuring the expression level of a MECP2 protein or a polynucleotide encoding the MECP2 protein in a sample separated from a subject; And

b) determining that the expression level of the MECP2 protein selected in a) above or the polynucleotide encoding the same is degenerative brain disease, compared to the control, and providing a gene detection method for providing degenerative brain disease diagnostic information do.

The sample may be brain tissue.

According to another aspect of the present invention, there is provided a method for detecting a mRNA expression vector comprising the steps of: a) treating a test substance with mRNA expressing cells of MECP2;

b) selecting a test substance which increases the expression level of the mRNA selected in the step a) compared to the control group.

MECP2, a gene responsible for degenerative brain diseases, was expressed through the virus as a therapeutic substance, effectively transmitted to the brain, and increased MECP2 in the brain. Accordingly, the composition of the present invention can be used to treat degenerative brain diseases, especially Alzheimer's syndrome, caused by amyloid beta, and to improve or ameliorate the symptoms of cognitive dysfunction and sociability deficiency caused by Alzheimer's syndrome.

FIG. 1 is a diagram showing a series of steps for preparing an animal model of Alzheimer's disease according to Experimental Example 1 of the present invention. FIG. 1 is a brain structure of an animal model showing an injection position of amyloid beta.
FIG. 2A is a brain structure diagram showing a brain-extracted region from an Alzheimer's animal model according to Experimental Example 2 of the present invention. FIG.
FIG. 2B shows the result of performing brain tissue extraction from an animal model of Alzheimer's disease according to Experimental Example 2 of the present invention.
3 is a photograph of a mechanism for a passive avoidance experiment according to Experimental Example 3 of the present invention.
FIG. 4 is a graph showing cognitive function measured through passive avoidance experiments of each group (control, AD model) according to Experimental Example 3 of the present invention.
FIG. 5 is a graph showing cognitive function measured by passive avoidance experiment of each group (control, AD model, MECP2 OE) according to Experimental Example 3 of the present invention.
FIG. 6 is a graph showing the tager 1, target 2, and sending time indicating the social preference index of each group (control, AD model) from the experiment 4 of the present invention.
FIG. 7 is a graph showing the degree of sniffing with tager1 and target2 representing the social preference index of each group (control, AD model) according to Experimental Example 3 of the present invention.
FIG. 8 is a graph showing tager 1, target 2, and sending time indicating the social preference index of each group (control, AD model, Over) in the experiment of the present invention.
FIG. 9 is a graph showing the degree of sniffing with tager1 and target2 representing the social preference index of each group (control, AD model, Over) according to Experimental Example 3 of the present invention.
10 is a graph showing the influence of each test group on the suppression of the preceding stimulus in the acoustic stimulus response according to Experimental Example 5 of the present invention.

Hereinafter, various aspects and various embodiments of the present invention will be described in more detail.

One aspect of the present invention relates to a pharmaceutical composition for preventing or treating a degenerative brain disease comprising the MECP2 protein of SEQ ID NO: 1 and a polynucleotide encoding the MECP2 protein as an active ingredient.

MECP2 is a protein that specifically inhibits the transcription of a methylated promoter. When mutation occurs in MECP2, it is known that RET's syndrome, which is a rare disease of the nervous system, is developed. However, the relationship between MECP2 and degenerative brain diseases such as Alzheimer's disease There is no report on the therapeutic or prophylactic effect of Alzheimer's dementia due to accumulation of amyloid beta in particular. Under these circumstances, the present inventors have found a correlation between MECP2 protein and Alzheimer's dementia induced by the injection and accumulation of amyloid beta, and have found that the MECP2 protein, a nucleotide encoding the same, or a recombinant vector containing the MECP2 protein, Or treatments can be said to be about new uses.

The MECP2 protein may comprise the MECP2 protein of SEQ ID NO: 1 and functional equivalents and functional derivatives thereof, which are proteins having substantially equivalent physiological activity.

The polynucleotide encoding MECP2 in the present invention is characterized in that it comprises a nucleotide sequence encoding the MECP2 protein or a functional equivalent thereof, and the nucleotide sequence includes all of DNA, cDNA, and RNA sequences. Preferably, the MECP2 gene is represented by the nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 1, and most preferably the nucleotide sequence of SEQ ID NO: 2.

The degenerative brain diseases are specifically Parkinson's disease, Alzheimer's disease (senile dementia), stroke, Lou Gehrig's disease, Pick's disease, Creutzfeldt Jakob disease, Huntington's disease, progressive supranuclear palsy, spinal cord cerebellar atrophy, cerebellar atrophy, multiple sclerosis, And amyotrophic schizophrenia. More specifically, it may be Alzheimer's disease caused by accumulation of amyloid beta.

In a specific embodiment of the present invention, the inventors produced an animal model of Alzheimer's dementia induced by administering amyloid beta to the ventricle. The produced Alzheimer's dementia animal model found that the injection of amyloid beta increased the level of MECP2 expression in brain tissue in early Alzheimer's disease.

As described above, MECP2 protein is known to be a causative agent of Rett syndrome, which is a rare disease among neurological diseases. However, the relationship between amyloid beta and Alzheimer's disease has not been reported. Therefore, the present inventors confirmed that the increase of MECP2 in the ventricles due to the accumulation of amyloid beta is associated with Alzheimer's dementia symptoms such as cognitive dysfunction and sociability deficiency, and ultimately, it is involved in developing Alzheimer's dementia.

First, it was demonstrated that mice injected with amyloid beta directly into the ventricles had early characteristics of Alzheimer ' s dementia such as decreased cognitive dysfunction and lack of sociality. This indicates that Alzheimer's dementia was induced through the injection of amyloid beta from the animal model.

In addition, by administering the MECP2 protein of the present invention or a polynucleotide encoding the same or a recombinant virus containing the MECP2 protein, the MECP2 protein is increased in an animal model that induces Alzheimer's dementia, and the mortality is increased, Avoidance, sociality and pre - stimulation inhibition experiments were performed to confirm that the cognitive function was improved and the lack of sociality was alleviated. Therefore, the MECP2 protein of the present invention, the polynucleotide encoding the same, or the recombinant virus comprising the MECP2 protein or the polynucleotide encoding the MECP2 protein of the present invention can be effectively used for the improvement and therapeutic effect of Alzheimer's disease.

The term "prophylactic" in the present invention refers to any action in which the administration of the pharmaceutical composition of the present invention inhibits or delays the onset of degenerative brain disease, particularly Alzheimer ' s dementia, or alleviates, ameliorates or alleviates symptoms. In the present invention, the term "treatment" refers to all actions that are beneficially altered by the administration of the pharmaceutical composition of the present invention, such as improving, alleviating or alleviating the symptoms of the disease.

The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier. The term " pharmaceutically acceptable "as used herein means that the composition is free of toxicity to cells or humans exposed to the composition. Compositions comprising a pharmaceutically acceptable carrier can be of various oral or parenteral formulations. In the case of formulation, it can be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, It may be at least one selected from the group consisting of polyvinylpyrrolidone, physiological saline, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol and liquid paraffin, But it is not limited thereto, and any conventional carrier, excipient or diluent may be used. These components may be added to the active component of the MECP2 (methyl CpG binding protein 2) protein of SEQ ID NO: 1 or a polynucleotide encoding the same independently or in combination.

The pharmaceutical composition of the present invention can be administered through a route commonly used in gene therapy, and parenteral administration is preferred. For example, administration by intravenous administration, intraperitoneal administration, intramuscular administration, subcutaneous administration, local administration can do. The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with another therapeutic agent, and may be administered sequentially or simultaneously with a conventional therapeutic agent.

Solid formulations for oral administration may include tablet pills, powders, granules, capsules and the like, which may contain one or more excipients, such as starch, calcium carbonate, sucrose or lactose, lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.

In addition, the pharmaceutical composition of the present invention may be formulated into tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations and suppositories And can have any one of the formulations selected.

The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount. There is no particular restriction on the dosage, and it may vary depending on the body's absorption, body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, severity of disease and the like. The pharmaceutical composition of the present invention is prepared in consideration of an effective dose range, and the unit dosage formulations thus formulated are used according to the judgment of the expert who monitors or observes the administration of the drug as required, and a specialized dosage regimen Or several times at predetermined time intervals. Preferably, the pharmaceutical composition of the present invention may be administered at a dose of 0.5 to 5000 mg / kg, preferably 50 to 500 mg / kg, more preferably 50 mg / kg, per day based on the amount of the camphor extract , And the administration may be carried out once a day or several times.

Further, the mixing amount of the active ingredient may be appropriately changed depending on the intended use (prevention, health or therapeutic treatment). As a specific example, the MECP2 (methyl CpG binding protein 2) protein of SEQ ID NO: 1 of the present invention or the polynucleotide encoding the MECP2 protein of the present invention is contained in an amount of 5% by weight or less, preferably 1% by weight or less . However, when it is intended for health and hygiene purposes or for the purpose of controlling health, it can be added in an amount below the above range, and there is no problem in terms of safety. Therefore, the active ingredient can be used in an amount exceeding the above range have.

There is no particular limitation on the kind of the food. Examples of the food to which the MECP2 (methyl CpG binding protein 2) protein of SEQ ID NO: 1 of the present invention or the polynucleotide encoding the same can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, Noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, vitamin complexes, and the like.

When the food composition of the present invention is prepared as a beverage, it may contain additional ingredients such as various flavors or natural carbohydrates such as ordinary beverages. Examples of the natural carbohydrate include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharin and aspartame, and the like. The natural carbohydrate is contained in an amount of 0.01 to 10% by weight, preferably 0.01 to 0.1% by weight based on the total weight of the food composition of the present invention.

In addition to the above, the food composition of the present invention may contain various nutrients, vitamins, electrolytes, flavors, colorants, pectic acid and salts thereof, alginic acid and its salts, organic acids, protective colloid thickeners, pH adjusters, stabilizers, preservatives, glycerin, , Carbonating agents used in carbonated beverages, and the like. In addition, the compositions of the present invention may include flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination.

The proportion of the above additives is not limited to a great extent, but may be in the range of 0.01 to 0.1% by weight based on the total weight of the food composition of the present invention.

Another aspect of the present invention is a method for preventing or treating a degenerative brain disease comprising a recombinant vector comprising the MECP2 protein of SEQ ID NO: 1 and a polynucleotide encoding the same, a recombinant cell comprising the recombinant vector, or a mixture thereof as an active ingredient ≪ / RTI >

MECP2 is a protein that specifically inhibits the transcription of a methylated promoter. When mutation occurs in MECP2, it is known that RET's syndrome, which is a rare disease of the nervous system, is developed. However, the relationship between MECP2 and degenerative brain diseases such as Alzheimer's disease There is no report on the therapeutic or prophylactic effect of Alzheimer's dementia due to accumulation of amyloid beta in particular. Under these circumstances, the present inventors have found a correlation between MECP2 protein and Alzheimer's dementia induced by the injection and accumulation of amyloid beta, and have found that the MECP2 protein, a nucleotide encoding the same, or a recombinant vector containing the MECP2 protein, Or treatments can be said to be about new uses.

The MECP2 protein may comprise the MECP2 protein of SEQ ID NO: 1 and functional equivalents and functional derivatives thereof, which are proteins having substantially equivalent physiological activity.

The polynucleotide encoding MECP2 in the present invention is characterized in that it comprises a nucleotide sequence encoding the MECP2 protein or a functional equivalent thereof, and the nucleotide sequence includes all of DNA, cDNA, and RNA sequences. Preferably, the MECP2 gene is represented by the nucleotide sequence encoding the amino acid sequence of SEQ ID NO: 1, and most preferably the nucleotide sequence of SEQ ID NO: 2.

The degenerative brain diseases are specifically Parkinson's disease, Alzheimer's disease (senile dementia), stroke, Lou Gehrig's disease, Pick's disease, Creutzfeldt Jakob disease, Huntington's disease, progressive supranuclear palsy, spinal cord cerebellar atrophy, cerebellar atrophy, multiple sclerosis, And amyotrophic schizophrenia. More specifically, it may be Alzheimer's disease caused by accumulation of amyloid beta.

In a specific embodiment of the present invention, the inventors produced an animal model of Alzheimer's dementia induced by administering amyloid beta to the ventricle. The produced Alzheimer's dementia animal model found that MECP2 disappeared in the ventricle when early Alzheimer's disease, due to the injection of amyloid beta.

As described above, MECP2 protein is known to be a causative agent of Rett syndrome, which is a rare disease among neurological diseases. However, the relationship between amyloid beta and Alzheimer's disease has not been reported. Thus, the present inventors confirmed that the decrease of MECP2 in the ventricle due to the accumulation of amyloid beta causes symptoms of Alzheimer's dementia such as cognitive dysfunction and sociability deficiency, and ultimately it is involved in developing Alzheimer's dementia.

First, it was demonstrated that mice injected with amyloid beta directly into the ventricle had early characteristics of Alzheimer's dementia such as cognitive dysfunction, impaired motor ability and lack of sociality. This indicates that Alzheimer's dementia was induced through the injection of amyloid beta from the animal model.

In addition, by administering the MECP2 protein of the present invention or a polynucleotide encoding the same or a recombinant virus containing the MECP2 protein, the MECP2 protein is increased in an animal model that induces Alzheimer's dementia, and the mortality is increased, Avoidance, sociality and anticipatory stimulation inhibition experiments were performed to confirm that cognitive function was improved, social deficits were alleviated, and cognition and motor function were improved. Therefore, the MECP2 protein of the present invention, the polynucleotide encoding the same, or the recombinant virus comprising the MECP2 protein or the polynucleotide encoding the MECP2 protein of the present invention can be effectively used for the improvement and therapeutic effect of Alzheimer's disease.

As used herein, the term "vector" refers to any medium for cloning and / or transfer of a base into a host cell. A vector can be a replicon that can bring about the replication of a joined fragment of another DNA fragment. Refers to any genetic unit (e.g., a plasmid, phage, cosmid, chromosome, or virus) that functions in vivo as an autologous unit of DNA replication, that is, . The term "vector" includes viral and non-viral mediators for introducing a base into a host cell in vitro, in vitro or in vivo.

The viral vector may specifically be a viral vector loaded on a viral vector selected from the group consisting of adenoassociated virus (AAV), adenovirus, lentivirus, retrovirus, vaccinia virus, and herpes simplex virus Recombinant viruses can be used.

A "viral vector" of the present invention is a viral vector capable of delivering a therapeutic gene or genetic material to a desired cell, tissue and / or organ.

The recombinant vector or recombinant cell of the present invention can prevent or treat amyloid beta-induced Alzheimer's dementia disease with improved efficacy by expressing the MECP2 gene.

The term "prophylactic" in the present invention refers to any action in which the administration of the pharmaceutical composition of the present invention inhibits or delays the onset of degenerative brain disease, particularly Alzheimer ' s dementia, or alleviates, ameliorates or alleviates symptoms. In the present invention, the term "treatment" refers to all actions that are beneficially altered by the administration of the pharmaceutical composition of the present invention, such as improving, alleviating or alleviating the symptoms of the disease.

The pharmaceutical composition of the present invention may further comprise a pharmaceutically acceptable carrier. The term " pharmaceutically acceptable "as used herein means that the composition is free of toxicity to cells or humans exposed to the composition. Compositions comprising a pharmaceutically acceptable carrier can be of various oral or parenteral formulations. In the case of formulation, it can be prepared using diluents or excipients such as fillers, extenders, binders, humectants, disintegrants, surfactants and the like which are usually used. Examples of the carrier, excipient and diluent include lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, acacia rubber, alginate, gelatin, calcium phosphate, calcium silicate, cellulose, methylcellulose, microcrystalline cellulose, It may be at least one selected from the group consisting of polyvinylpyrrolidone, physiological saline, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil, dextrin, calcium carbonate, propylene glycol and liquid paraffin, But it is not limited thereto, and any conventional carrier, excipient or diluent may be used. These components may be added to the active component of the MECP2 (methyl CpG binding protein 2) protein of SEQ ID NO: 1 or a polynucleotide encoding the same independently or in combination.

The pharmaceutical composition of the present invention can be administered through a route commonly used in gene therapy, and parenteral administration is preferred. For example, administration by intravenous administration, intraperitoneal administration, intramuscular administration, subcutaneous administration, local administration can do. The pharmaceutical composition of the present invention may be administered as an individual therapeutic agent or in combination with another therapeutic agent, and may be administered sequentially or simultaneously with a conventional therapeutic agent.

Solid formulations for oral administration may include tablet pills, powders, granules, capsules and the like, which may contain one or more excipients, such as starch, calcium carbonate, sucrose or lactose, lactose, gelatin, and the like. In addition to simple excipients, lubricants such as magnesium stearate, talc, and the like may also be used. Liquid preparations for oral administration include suspensions, solutions, emulsions, syrups and the like. Various excipients such as wetting agents, sweeteners, fragrances, preservatives and the like may be included in addition to water and liquid paraffin, which are simple diluents commonly used. have. Formulations for parenteral administration may include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried preparations, and suppositories. Examples of the non-aqueous solvent and the suspending agent include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate. As the base of the suppository, witepsol, macrogol, tween 61, cacao paper, laurin, glycerogelatin and the like can be used.

In addition, the pharmaceutical composition of the present invention may be formulated into tablets, pills, powders, granules, capsules, suspensions, solutions, emulsions, syrups, sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations and suppositories And can have any one of the formulations selected.

The pharmaceutical composition of the present invention can be administered in a pharmaceutically effective amount. There is no particular restriction on the dosage, and it may vary depending on the body's absorption, body weight, age, sex, health condition, diet, administration time, administration method, excretion rate, severity of disease and the like. The pharmaceutical composition of the present invention is prepared in consideration of an effective dose range, and the unit dosage formulations thus formulated are used according to the judgment of the expert who monitors or observes the administration of the drug as required, and a specialized dosage regimen Or several times at predetermined time intervals. Preferably, the pharmaceutical composition of the present invention may be administered at a dose of 0.5 to 5000 mg / kg, preferably 50 to 500 mg / kg, more preferably 50 mg / kg, per day based on the amount of the camphor extract , And the administration may be carried out once a day or several times.

When the effective ingredient of the present invention is a recombinant vector, it specifically contains 0.01 to 500 mg, more specifically 0.1 to 300 mg, and in the case of the recombinant virus containing the recombinant vector, specifically, 10 ³ to 10 ¹² IU ( 10 to 10 < 10 ^> PFU), more specifically from 10 ⁵ to 10 ¹⁰ IU, but is not limited thereto.

When the effective ingredient of the present invention is a cell, it specifically contains 10 ³ to 10 ⁸ , more specifically 10 ⁴ to 10 ⁷ , but is not limited thereto.

The effective dose of the composition of the present invention is 0.05 to 12.5 mg / kg for recombinant vector per 1 kg of body weight, 10 ⁷ to 10 ¹¹ viral particles (10 ⁵ to 10 ⁹ IU) / kg for recombinant virus, is 10 ³ to 10 ⁶ for cells / ㎏ and, specifically, when the recombinant vector is 0.1 to 10 ㎎ / ㎏, when the recombinant virus is 10 ⁸ to 10 ¹⁰ particles (10 ⁶ to 10 ⁸ IU) / ㎏, cell 10 ² to 10 ⁵ cells / kg, and can be administered 2 to 3 times a day. The composition is not necessarily limited to this, and may vary depending on the condition and the degree of onset of the patient.

Further, the mixing amount of the active ingredient may be appropriately changed depending on the intended use (prevention, health or therapeutic treatment). As a specific example, the MECP2 (methyl CpG binding protein 2) protein of SEQ ID NO: 1 of the present invention or the polynucleotide encoding the MECP2 protein of the present invention is contained in an amount of 5% by weight or less, preferably 1% by weight or less . However, when it is intended for health and hygiene purposes or for the purpose of controlling health, it can be added in an amount below the above range, and there is no problem in terms of safety. Therefore, the active ingredient can be used in an amount exceeding the above range have.

There is no particular limitation on the kind of the food. Examples of the food to which the MECP2 (methyl CpG binding protein 2) protein of SEQ ID NO: 1 of the present invention or the polynucleotide encoding the same can be added include meat, sausage, bread, chocolate, candy, snacks, confectionery, Noodles, gums, dairy products including ice cream, various soups, beverages, tea, drinks, alcoholic beverages, vitamin complexes, and the like.

When the food composition of the present invention is prepared as a beverage, it may contain additional ingredients such as various flavors or natural carbohydrates such as ordinary beverages. Examples of the natural carbohydrate include monosaccharides such as glucose and fructose; Disaccharides such as maltose and sucrose; Natural sweeteners such as dextrin and cyclodextrin, synthetic sweeteners such as saccharin and aspartame, and the like. The natural carbohydrate is contained in an amount of 0.01 to 10% by weight, preferably 0.01 to 0.1% by weight based on the total weight of the food composition of the present invention. In addition to the above, the food composition of the present invention may contain various nutrients, vitamins, electrolytes, , A colorant, a pectic acid and its salt, an alginic acid and its salt, an organic acid, a protective colloid thickener, a pH adjusting agent, a stabilizer, a preservative, a glycerin, an alcohol and a carbonating agent used in a carbonated drink. In addition, the compositions of the present invention may include flesh for the production of natural fruit juices, fruit juice drinks and vegetable drinks. These components may be used independently or in combination.

The proportion of the above additives is not limited to a great extent, but may be in the range of 0.01 to 0.1% by weight based on the total weight of the food composition of the present invention.

Another aspect of the present invention relates to a composition for the diagnosis of degenerative brain diseases comprising a primer, a probe or an antibody for detecting MECP2 protein and a polynucleotide encoding the MECP2 protein. By using the composition, Degenerative brain disease Specifically, Alzheimer's disease can be diagnosed.

In a specific embodiment of the present invention, the inventors produced an animal model of Alzheimer's dementia induced by administering amyloid beta to the ventricle. The produced Alzheimer's dementia animal model found that the injection of amyloid beta increased the level of MECP2 expression in brain tissue in early Alzheimer's disease.

The present inventors have demonstrated that the mice injected with amyloid beta directly into the ventricle have early characteristics of Alzheimer ' s dementia such as decreased cognitive dysfunction and lack of sociality. This indicates that Alzheimer's dementia was induced through the injection of amyloid beta from the animal model.

In conclusion, the increase in MECP2 is associated with degenerative brain diseases such as Alzheimer's disease, and abnormal growth of MECP2 can confirm degenerative brain diseases such as Alzheimer's disease.

According to the present invention, when the level of expression of the MECP2 protein and the polynucleotide encoding the MECP2 protein in the sample separated from the subject is increased, degenerative brain disease caused by accumulation or infusion of amyloid beta, in particular, Alzheimer's disease can be determined.

That is, the present invention provides a method for detecting a protein comprising the steps of: a) measuring the expression level of a MECP2 protein or a polynucleotide encoding the MECP2 protein in a sample separated from a subject; And

b) If the expression level of the MECP2 protein or the polynucleotide encoding the MECP2 protein selected in the above a) is increased as compared to the control group, it can be determined that the degenerative brain disease is a degenerative brain disease. have.

The expression level of the MECP2 protein or a polynucleotide encoding the MECP2 protein is not particularly limited as long as it is a method commonly used in the art.

Specifically, the expression level of the protein can be measured by immunoprecipitation, radioimmunoassay (RIA), enzyme immunoassay (ELISA), immunohistochemistry, RT-PCR, Western blotting and flow cytometry And can be measured by any one method selected from the group consisting of.

The polynucleotide encoding the MECP2 protein can be identified through the expression level of mRNA, and the mRNA expression level can be measured by reverse transcriptase polymerase chain reaction (RT-PCR), real-time PCR, And next-generation sequencing (NGS). ≪ / RTI >

In another aspect of the present invention, there is also provided a method of detecting a test substance, comprising the steps of: a) treating a test substance with an expression cell of a MECP2 protein or a polynucleotide encoding the same;

b) selecting a test substance which increases the expression level of the MECP2 protein or a polynucleotide encoding the MECP2 protein selected in step a) in comparison with the control group, thereby treating the degenerative brain disease treatment agent, specifically, the Alzheimer's disease caused by accumulation or injection of amyloid beta Screening of candidate therapeutic agents is possible.

The test substance may be any one selected from the group consisting of natural compounds, synthetic compounds, RNA, DNA, polypeptides, enzymes, proteins, ligands, antibodies, metabolites of antigens, bacteria or fungi, and bioactive molecules.

Hereinafter, the present invention will be described in more detail with reference to Examples and the like, but the scope and content of the present invention can not be construed to be limited or limited by the following Examples. It will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the spirit and scope of the present invention as set forth in the following claims. It is natural that it belongs to the claims.

In addition, the experimental results presented below only show representative experimental results of the embodiments and the comparative examples, and the respective effects of various embodiments of the present invention which are not explicitly described below will be specifically described in the corresponding part.

Example  1. Preparation of recombinant virus

The recombinant viruses according to the present invention were prepared using the following cleavage map.

Experimental Example  1. Animal models

end. Aβ _{1 to 42}  Ready

Peptides composed of 42 amino acids corresponding to human amyloid beta were synthesized. For their fiber formation, the amyloid beta peptide was dissolved in sterile PBS (with 10% DMSO) and incubated for 24 hours at 37 C before use.

I. Preparation of experimental animals and Alzheimer's animal model (AD model)

In this experiment, 8-week-old B6 male mice of about 25 to 30 g were prepared to be used as experimental animals. The experimental procedure was to take standard rodent diet and water as desired, and the animal care and use committee of IACUC Lt; / RTI >

The animals were allowed to adapt for one week, and animals observed for abnormal behavior were not used in this experiment. All experimental animals were allowed to drink water and feed freely under the condition of 12 hours of light and 12 hours of shading in a kennel capable of constant temperature and humidity during the experiment period.

Animals are anesthetized by intraperitoneal injection of ketamine and xylazine, and then prepare a stereotaxic frame (Narishige, Japan). All experiments attempted to minimize animal suffering. The amyloid beta was injected into the ventricle of the animal according to the Kim method (J. Alzheimers Dis. 2010 Kim). Each mouse was injected at a depth of 2.2 mm in the parietal lobe with a 50 μL Hamilton microsyringe with a 26-gauge needle. The injected dose is 5 [mu] L (Fig. 1).

Experimental Example  2. Tissue Dyeing ( Thioflavin  S staining) Experiment

end. Experimental group

In the present invention, two groups of animal models were prepared according to Experimental Example 1 in order to analyze the relationship between MECP2 and an animal model of Alzheimer's Dementia induced by Experimental Example 1. [

Group 1: Alzheimer's Disease-free, PBS-injected (control; control)

Group 2: A group that induced Alzheimer's dementia by injecting amyloid beta (AD model)

I. Tissue Dyeing Experiments and Results

Three days after the injection of amyloid beta, the animals were anesthetized with intraperitoneal injection of ketamine and xylazine and perfused with 4% paraformaldehyde (0.1 M phosphate buffer, pH 7.4). The brain is taken out and immersed in PBS containing 20% sucrose for one day, and a continuous coronal slice of 40 μm thickness is made using a freezing device. The sectioned tissue was stained with thioflavin S (Sigma-Aldrich) solution for 8 min. The cells were washed twice with 100% ethanol in 80% ethanol / water and mixed with distilled water for 10 min. (Tasai et al., JEM, 2007).

Immunologically labeled slides were digitized and recorded using a Leica DMR microscope (Leica Microsystems, Wetzlar, Germany) equipped with a CoolSNAP camera (Princeton, Trenton, NJ, USA).

FIG. 2A is a brain structure diagram showing a brain-extracted region from an animal model of Alzheimer's disease according to Experimental Example 2 of the present invention. FIG. 2B is a graph showing the brain structure of an Alzheimer's animal model according to Experimental Example 2 of the present invention, The results are shown in Fig.

As shown in Figs. 2a and 2b, the expression of MeCP2 protein was increased in the brain tissue of the Alzheimer's animal model.

Experimental Example  3. Passive avoidance experiment

end. Experimental animals and Experimental group

For the experiments of the present invention, the following experimental groups were set up and prepared according to Experimental Example 1. At least 10 rats of each group were used.

Group 1: Alzheimer's Disease-free, PBS-injected (control; control)

Group 2: A group that induced Alzheimer's dementia by injection of amyloid alpha (AD model)

Group 3: A recombinant virus of Example 1 was administered to overexpress MECP2 (MECP2 OE) followed by amyloid alpha injection to induce Alzheimer ' s dementia

I. Experimental methods and results

Three days after the injection of amyloid beta, passive avoidance experiment was performed. The manual evasive instrument is divided into two zones, each with light and dark areas, and the bottom is made of wire mesh. During training, each mouse is placed in a bright area, the door closes as soon as the mouse moves into the dark area, and a current of 0.1 mA is applied to the foot shock for 3 seconds. The test is performed one day after the training, and the time from when the mice are placed in the bright area to the dark zone again (maximum time is set to 600 seconds) (Fig. 3). This passive avoidance experiment can evaluate spatial learning and memory.

FIG. 4 is a graph showing a result of measuring a popular function through passive avoidance experiment of each group (control, AD model) according to Experimental Example 3 of the present invention. FIG. control, AD model, MECP2 OE).

All data were expressed as mean (S.E.M), and differences between the experimental groups were confirmed using Student's t-test. In the case of p> 0.05, it was judged that there was a statistical difference and it was marked with ****.

As shown in FIGS. 4 and 5, in the case of the normal animal model and the AD model, the Elapse time was confirmed to be shortened by more than two times, and thus, the ventral injection of the amyloid beta This marked reduction in Alzheimer's dementia can be confirmed (①).

However, when the recombinant virus of Example 1 was injected into the above Alzheimer's animal model, overexpression of MECP2 confirmed that the Elapse time was recovered more than twice as much as that of the AD model injected with PBS buffer solution ().

In summary, it was confirmed that Alzheimer's dementia can be induced from animals by injecting amyloid beta into the ventricle, and when overexpressing MECP2 through the recombinant virus of Example 1 of the present invention in the animal model of Alzheimer's dementia thus produced, (Memory) recovered to a level equivalent to that of a normal animal model, the recombinant virus according to the present invention can induce overexpression of MECP2 in the animal body, thereby causing amyloid beta-induced Alzheimer's dementia symptoms It can be seen that treatment and improvement can be remarkably performed.

Experimental Example  4. Social experiment

end. Experimental group

For the experiments of the present invention, the following experimental groups were set up and prepared according to Experimental Example 1. At least 10 rats of each group were used.

Group 1: Alzheimer's Disease-free, PBS-injected (control; control)

Group 2: A group that induced Alzheimer's dementia by injection of amyloid alpha (AD model)

Group 3: Administration of the recombinant virus of Example 1 to overexpress MECP2 (OVER) followed by injection of amyloid alpha to induce Alzheimer ' s dementia

I. Experimental methods and results

To assess sociality, tests were performed using three chamber social interaction tests. Specifically, the 3-chamber test measures the amount of time and sniffing of the animal model (control or AD model) between a familiar mouse (target1) and a new mouse (target2) by inserting a familiar mouse and a new mouse , And social preference index.

The interaction was defined as each time when the animal model was trying to smell an unfamiliar animal, with the nose pointing toward the unfamiliar animal and approaching the nose.

FIG. 6 is a graph showing tager 1 and target 2 representing the social preference index of each group (control, AD model) and sending time from 4 in the experiment of the present invention, and FIG. 7 is a graph This is a graph showing the degree of sniffing with tager1 and target2 indicating the social preference index of the group (control, AD model).

FIG. 8 is a graph showing tager 1 and target 2, which are representative of the social preference index of each group (control, AD model, Over), and the sending time from the experiment 4 of the present invention. , And sniffing with tager1 and target2, which indicate the social preference index of each group (control, AD model, Over).

All data were expressed as mean (S.E.M), and differences between the experimental groups were confirmed using Student's t-test. In the case of p> 0.05, it was judged that there was a statistical difference and it was marked with ****.

As shown in FIGS. 6 and 7, normal animal models and AD models confirmed similar residence times in the familiar and new mice. On the contrary, the degree of interaction was significantly different between the normal animal model (control) and the Alzheimer's animal model (AD model). Specifically, the AD model of the Alzheimer's model showed significantly less interaction with the familiar mouse than the normal animal model (control), and eventually it was found to be reduced to the same degree as the unfamiliar mice.

In other words, it was confirmed that cognitive function was significantly reduced in the animal model through injection of the ventricle of amyloid beta, resulting in a problem in social behavior, and it can be confirmed that Alzheimer's dementia was developed (①, ②).

As shown in FIGS. 8 and 9, when the overexpression of MECP2 using the recombinant virus in the Alzheimer's animal model (Over), the time spent with the mouse familiar with the PBS model buffer And the degree of interaction increased by 40 ~ 50% (③, ④). This is higher than the normal animal model (control).

In other words, when the overexpression of MECP2 in the AD model induced by Alzheimer's dementia (AD model) overexpressed MECP2 (Over), it was confirmed that the defective sociability deficiency symptom recovered to a remarkably higher level than the normal animal model. It can be seen that the symptoms of Alzheimer's dementia caused by amyloid beta can be remarkably treated and improved by inducing overexpression of MECP2 by using the virus.

Experimental Example  5. Pre-stimulation inhibition experiment

In this experiment, the extent to which the startle response of the rats was affected by the preceding beep was measured and evaluated. Specifically, the experimental apparatus for the experiment consisted of a chamber made of transparent plexiglass and placed on a platform; The platform was placed inside a sound insulation chamber. High-frequency sonic columns delivering auditory stimuli were placed 2 cm from the platform. The animal's surprise was caused by the vibration of the platform, which was measured by a record of an analog converter and a computer. The level of the background noise was made to be 65 dB. Each animal receives three stimuli, a simple experiment (pulse) of 50 ms duration and a pulsed pre stimulation (pre-pulse) of 120 dB or 20 ms duration and stimulation of 74, 82 and 90 dB, followed by 30 ms followed by 50 ms period and a pulse stimulus of 120 dB. The time interval between repeated pulses combined with pulse stimulation or before the pulse was 10 seconds. The surprise suppression corresponding to the pulse pre-post-pulse stimulus was calculated as a percentage of the surprise interval corresponding to a single pulse stimulus. At this time, it can be estimated that the lower the% PPI of the animal, the lower the cognitive function (sensory gating).

FIG. 10 is a graph showing the effect of each test group on the suppression of the leading stimulus in the acoustic stimulus response according to Experimental Example 5 of the present invention. According to the graph, the animal model (AD model) control) is lower than the total surprise suppression. That is, the administration of amyloid beta inhibited the stimulation response, and the CNS (central nervous system) ability of the sensory stimulation filter in the animal model was lowered.

In other words, it was confirmed that the cognitive function (sensory exercise gating) was significantly reduced in the animal model through injection of the ventricle of the amyloid beta, and it can be confirmed that the dementia of Alzheimer's disease was effectively developed.

<110> KOREA INSTITUTE OF SCIENCE AND TECHNOLOGY <120> Composition comprising MECP2 protein or polynucleotide encoding          the MECP2 for prevention and treatment of neurodegenerative          disease <130> HPC7732 <160> 2 <170> KoPatentin 3.0 <210> 1 <211> 484 <212> PRT <213> Artificial Sequence <220> <223> MECP2 <400> 1 Met Val Ala Gly Met Leu Gly Leu Arg Glu Glu Lys Ser Glu Asp Gln   1 5 10 15 Asp Leu Gln Gly Leu Arg Asp Lys Pro Leu Lys Phe Lys Lys Ala Lys              20 25 30 Lys Asp Lys Lys Glu Asp Lys Glu Gly Lys His Glu Pro Leu Gln Pro          35 40 45 Ser Ala His His Ser Ala Glu Pro Ala Glu Ala Gly Lys Ala Glu Thr      50 55 60 Ser Glu Ser Gly Ser Ser Ala Ser Ala Ser  65 70 75 80 Pro Lys Gln Arg Arg Ser Ile Ile Arg Asp Arg Gly Pro Met Tyr Asp                  85 90 95 Asp Pro Thr Leu Pro Glu Gly Trp Thr Arg Lys Leu Lys Gln Arg Lys             100 105 110 Ser Gly Arg Ser Ala Gly Lys Tyr Asp Val Tyr Leu Ile Asn Pro Gln         115 120 125 Gly Lys Ala Phe Arg Ser Lys Val Glu Leu Ile Ala Tyr Phe Glu Lys     130 135 140 Val Gly Asp Thr Ser Leu Asp Pro Asn Asp Phe Asp Phe Thr Val Thr 145 150 155 160 Gly Arg Gly Ser Pro Ser Arg Arg Glu Gln Lys Pro Pro Lys Lys Pro                 165 170 175 Lys Ser Pro Lys Ala Pro Gly Thr Gly Arg Gly Arg Gly Arg Pro Lys             180 185 190 Gly Ser Gly Thr Gly Arg Pro Lys Ala Ala Ala Ser Glu Gly Val Gln         195 200 205 Val Lys Arg Val Leu Glu Lys Ser Pro Gly Lys Leu Val Val Lys Met     210 215 220 Pro Phe Gln Ala Ser Pro Gly Gly Lys Gly Gly Gly Gly Gly Ala Thr 225 230 235 240 Thr Ser Ala Gln Val Met Val Ile Lys Arg Pro Gly Arg Lys Arg Lys                 245 250 255 Ala Glu Ala Asp Pro Gln Ala Ile Pro Lys Lys Arg Gly Arg Lys Pro             260 265 270 Gly Ser Val Val Ala Ala Ala Ala Glu Ala Lys Lys Lys Ala Val         275 280 285 Lys Glu Ser Ser Ile Arg Ser Val His Glu Thr Val Leu Pro Ile Lys     290 295 300 Lys Arg Lys Thr Arg Glu Thr Val Ser Ile Glu Val Lys Glu Val Val 305 310 315 320 Lys Pro Leu Leu Val Ser Thr Leu Gly Glu Lys Ser Gly Lys Gly Leu                 325 330 335 Lys Thr Cys Lys Ser Pro Gly Arg Lys Ser Lys Glu Ser Ser Pro Lys             340 345 350 Gly Arg Ser Ser Ser Ser Ser Pro Pro Lys Lys Glu His His His         355 360 365 His His His His Ser Glu Ser Thr Lys Ala Pro Met Pro Leu Leu Pro     370 375 380 Ser Pro Pro Pro Glu Pro Glu Ser Ser Glu Asp Pro Ile Ser Pro 385 390 395 400 Pro Glu Pro Gln Asp Leu Ser Ser Ser Cys Lys Glu Glu Lys Met                 405 410 415 Pro Arg Gly Gly Ser Leu Glu Ser Asp Gly Cys Pro Lys Glu Pro Ala             420 425 430 Lys Thr Gln Pro Met Ala Thr Thr Thr Thr Val Ala Glu Lys Tyr         435 440 445 Lys His Arg Gly Glu Gly Glu Arg Lys Asp Ile Val Ser Ser Ser Met     450 455 460 Pro Arg Pro Asn Arg Glu Glu Pro Val Asp Ser Arg Thr Pro Val Thr 465 470 475 480 Glu Arg Val Ser                 <210> 2 <211> 1455 <212> DNA <213> Artificial Sequence <220> <223> MECP2 <400> 2 atggtagctg ggatgttagg gctcagggag gaaaagtcag aagaccagga tctccagggc 60 ctcagagaca agccactgaa gtttaagaag gcgaagaaag acaagaagga ggacaaagaa 120 ggcaagcatg agccactaca accttcagcc caccattctg cagagccagc agaggcaggc 180 aaagcagaaa catcagaaag ctcaggctct gccccagcag tgccagaagc ctcggcttcc 240 cccaaacagc ggcgctccat tatccgtgac cggggaccta tgtatgatga ccccaccttg 300 cctgaaggtt ggacacgaaa gcttaaacaa aggaagtctg gccgatctgc tggaaagtat 360 gatgtatatt tgatcaatcc ccagggaaaa gcttttcgct ctaaagtaga attgattgca 420 tactttgaaa aggtgggaga cacctccttg gaccctaatg attttgactt cacggtaact 480 gggagaggga gcccctccag gagagagcag aaaccaccta agaagcccaa atctcccaaa 540 gctccaggaa ctggcagggg tcggggacgc cccaaaggga gcggcactgg gagaccaaag 600 gcagcagcat cagaaggtgt tcaggtgaaa agggtcctgg agaagagccc tgggaaactt 660 gttgtagaga tgcctttcca agcatcgcct gggggtaagg gtgagggagg tggggctacc 720 acatctgccc aggtcatggt gatcaaacgc cctggcagaa agcgaaaagc tgaagctgac 780 ccccaggcca ttcctaagaa acggggtaga aagcctggga gtgtggtggc agctgctgca 840 gctgaggcca aaaagaaagc cgtgaaggag tcttccatac ggtctgtgca tgagactgtg 900 ctccccatca agaagcgcaa gacccgggag acggtcagca tcgaggtcaa ggaagtggtg 960 aagcccctgc tggtgtccac ccttggtgag aaaagcggga agggactgaa gacctgcaag 1020 agccctgggc gtaaaagcaa ggagagcagc cccaaggggc gcagcagcag tgcctcctcc 1080 ccacctaaga aggagcacca tcatcaccac catcactcag agtccacaaa ggcccccatg 1140 ccactgctcc catccccacc cccacctgag cctgagagct ctgaggaccc catcagcccc 1200 cctgagcctc aggacttgag cagcagcatc tgcaaagaag agaagatgcc ccgaggaggc 1260 tcactggaaa gcgatggctg ccccaaggag ccagctaaga ctcagcctat ggtcgccacc 1320 actaccacag ttgcagaaaa gtacaaacac cgaggggagg gagagcgcaa agacattgtt 1380 tcatcttcca tgccaaggcc aaacagagag gagcctgtgg acagccggac gcccgtgacc 1440 gagagagtta gctga 1455

Claims (9)

A pharmaceutical composition for preventing or treating a degenerative brain disease comprising an MECP2 (methyl CpG binding protein 2) protein of SEQ ID NO: 1 or a polynucleotide encoding the same. The method according to claim 1,
The degenerative brain disease is selected from the group consisting of Parkinson's disease, Alzheimer's dementia (senile dementia), stroke, Lou Gehrig's disease, Pick's disease, Creutzfeldt Jakob disease, Huntington's disease, progressive supranuclear palsy, spinal cord cerebellar atrophy, cerebellar atrophy, Wherein the compound is selected from the group consisting of depressive disorder, depressive disorder, and depressive disorder. A pharmaceutical composition for the prevention or treatment of degenerative brain diseases comprising as an active ingredient a recombinant vector expressing a gene encoding MECP2 (methyl CpG binding protein 2) of SEQ ID NO: 1, a recombinant cell comprising the recombinant vector, or a mixture thereof . The method of claim 3,
The degenerative brain disease is selected from the group consisting of Parkinson's disease, Alzheimer's dementia (senile dementia), stroke, Lou Gehrig's disease, Pick's disease, Creutzfeldt Jakob disease, Huntington's disease, progressive supranuclear palsy, spinal cord cerebellar atrophy, cerebellar atrophy, Wherein the compound is selected from the group consisting of insulin resistance, insulin resistance, and insomnia. The method of claim 3,
Wherein the degenerative brain disease is Alzheimer &apos; s disease caused by amyloid beta accumulation. A composition for diagnosing a degenerative brain disease comprising a primer, a probe or an antibody for detecting the MECP2 protein according to claim 1 and a polynucleotide encoding the same. a) measuring the level of expression of a MECP2 protein or a polynucleotide encoding the same in a sample isolated from a subject; And
b) determining that the degenerative brain disease is a degenerative brain disease if the expression level of the MECP2 protein selected in a) above or a polynucleotide encoding the same is increased compared to the control group. 8. The method of claim 7,
Wherein the sample is a brain tissue. a) treating the test substance with the mRNA expressing cells of MECP2; And
b) selecting a test substance that increases the expression level of the mRNA selected in step a) compared to the control group.

Images