WO2024080440A1 - Composition pour la prévention ou le traitement de troubles neurodégénératifs, comprenant le peptide humanine utilisé comme principe actif - Google Patents

Composition pour la prévention ou le traitement de troubles neurodégénératifs, comprenant le peptide humanine utilisé comme principe actif Download PDF

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WO2024080440A1
WO2024080440A1 PCT/KR2022/018471 KR2022018471W WO2024080440A1 WO 2024080440 A1 WO2024080440 A1 WO 2024080440A1 KR 2022018471 W KR2022018471 W KR 2022018471W WO 2024080440 A1 WO2024080440 A1 WO 2024080440A1
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disease
administration
composition
clause
parkinson
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김경화
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동아대학교 산학협력단
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system 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

Definitions

  • the purpose of the present invention is to provide a composition for preventing or treating degenerative brain diseases containing humanin peptide as an active ingredient.
  • Neurodegenerative disorders are diseases that cause various symptoms as degenerative changes occur in nerve cells of the central nervous system.
  • Representative degenerative brain diseases include Alzheimer's disease, Parkinson's disease, and progressive supranuclear disease.
  • Paralysis Progressive supranuclear palsy
  • Multiple system strophy Olivopontocerebellar atrophy (OPCA)
  • Shy-Drager syndrome Striatonigral degeneration
  • Huntington's disease amyotrophic lateral sclerosis (ALS), Essential tremor, Cortico-basal ganlionic degeneration, Diffuse Lewy body disease ), Parkinson-ALS-dementia complex of Guam, Pick's disease, etc.
  • ALS amyotrophic lateral sclerosis
  • Essential tremor Cortico-basal ganlionic degeneration
  • Diffuse Lewy body disease Diffuse Lewy body disease
  • Parkinson-ALS-dementia complex of Guam Pick's disease, etc.
  • Parkinson's disease is a degenerative neurological disorder characterized by loss of dopaminergic neurons in the substantia nigra.
  • Existing treatment methods for Parkinson's disease include oral treatment using levodopa drugs, dopamine agonists, anticholinergics, COMT, and MAO-B enzyme inhibitors. These are drugs designed to supplement dopamine substances or mimic the action of dopamine. They cannot prevent the disease from worsening and cause serious problems such as dyskinesia, nausea, and delusions, so the development of a treatment for Parkinson's disease is urgent.
  • a key hurdle in developing treatments for degenerative brain diseases such as Parkinson's disease is the difficulty in drug delivery due to the existence of the blood brain barrier (BBB).
  • BBB blood brain barrier
  • Existing therapeutic drugs cannot be efficiently delivered to the brain through the blood-brain barrier using systemic delivery.
  • the method of delivering drugs to the brain by bypassing the blood-brain barrier without systemic injection is known to deliver drugs to the brain via the trigeminal nerve through the nasal cavity, and is attracting attention as a new method of administering drugs to treat brain diseases.
  • Research on nasal-brain delivery through nasal injection of relatively small-sized peptides such as insulin has recently been conducted (PMID: 29970188), and such nasal-brain injection 1) enables efficient brain delivery of drugs, and 2) whole body. It is known to have the therapeutic effect of preventing the decomposition of drugs due to injection, and 3) reducing the side effects of drugs due to systemic injection.
  • Humanin is the first mitochondria-derived peptide (MDP) discovered. Humanin, first reported in 2001, was cloned from a cDNA library derived from surviving neurons of Alzheimer's patients and mapped to the mitochondrial genomic 16S ribosomal RNA locus (PMID: 11371646).
  • the receptors expressed on the cell surface are trimeric gp130, WSX1, and CNTF receptor (PMID: 19386761) and G protein-coupled formylpeptide receptor-like-1 (PMID: 15153530). ), etc., it is known that ligand-receptor binding can occur, thereby activating important signaling pathways within cells.
  • the fundamental mechanisms causing Parkinson's disease are not yet known, and treatment options are still very limited. Therefore, the present inventor found that the mitochondria-derived peptide Humanin peptide passes through the blood-brain barrier through the trigeminal nerve due to nasal inhalation. In addition, it was confirmed that dopaminergic neurodegeneration was suppressed by increasing the expression of oxidative stress defense genes.
  • the present invention was completed by confirming the therapeutic effect by injecting the mitochondria-derived peptide humanin of the present invention into a Parkinson's mouse model.
  • the purpose of the present invention is to provide a composition for preventing or treating degenerative brain diseases containing humanin peptide as an active ingredient.
  • an object of the present invention is to provide a method for preventing and treating degenerative brain diseases comprising administering to an individual a pharmaceutical composition of humanin peptide in a pharmaceutically effective amount.
  • the present invention provides a composition for preventing or treating degenerative brain diseases containing humanin peptide as an active ingredient.
  • the present invention provides a method for preventing and treating degenerative brain diseases comprising administering a pharmaceutical composition of humanin peptide in a pharmaceutically effective amount to a subject.
  • the humanin peptide of the present invention When the humanin peptide of the present invention was administered nasally to a mouse model of Parkinson's disease, it was confirmed that it was effectively delivered and distributed to the brain. In addition, it was confirmed that dopamine neuron expression increased and neuron damage was suppressed. In addition, it was confirmed to suppress nerve cell damage in a Parkinson's disease cell model, making it effective in treating Parkinson's disease, so it can be usefully used in related projects.
  • Figure 1 is a diagram showing a schedule for intranasal administration of the mouse model of the present invention.
  • Figure 2 is a diagram measuring the time for the mouse model to change direction to come down the bar by intranasally administering Humanin peptide to the neurotoxin MPTP Parkinson's disease mouse model.
  • Figure 3 is a diagram showing whether humanin peptide, a neurotoxin, was administered intranasally to a mouse model of Parkinson's disease, a neurotoxin MPTP, and the total time to descend the bar was measured to confirm whether or not there was improvement in movement.
  • Figure 4 shows fluorescent staining of Lectin, a vascular marker in the trigeminal nerve, after intranasal administration of FITC fluorescent Humanin peptide to a genetically modified mouse model overexpressing alpha-synuclein. It's a degree.
  • Figure 5 shows fluorescence staining of ⁇ -SMA, a marker for blood vessel wall cells in the trigeminal nerve, after intranasal administration of FITC fluorescent humanin peptide to a genetically modified mouse model overexpressing ⁇ -synuclein. It's a degree.
  • Figure 6 shows the area around the ventral tegmental area (VTA) where dopaminergic neurons are located and the cerebral aqueduct (AQ) after intranasal administration of FITC fluorescent Humanin peptide to a genetically modified mouse model overexpressing ⁇ -synuclein. ) This is a diagram confirming the distribution of the Humanin peptide discovered in ).
  • Figure 7 is a diagram confirming that there is no significant difference in the amount of circulating humanin peptide between normal patients and Parkinson's disease patients.
  • Figure 8 shows the inhibition of tyrosine hydroxylase (TH) enzyme damage to substantia nigra dopamine neurons after humanin peptide was intranasally injected for 8 days into a Parkinson's disease mouse model injected with the neurotoxin MPTP. This diagram shows the results of immunochemical staining.
  • TH tyrosine hydroxylase
  • Figure 9 shows tyrosine hydride with increased expression of cerebrostriatal dopamine neurons after intranasal injection of Humanin peptide (0.1 mg/kg, 5 mg/kg) for 8 days in a Parkinson's disease mouse model injected with the neurotoxin MPTP.
  • This is a diagram showing the tyrosine hydroxylase (TH) protein confirmed by immunoblot.
  • Figure 10 is a diagram showing neuronal damage through MTT assay after administration of Humanin peptide to a Parkinson's disease cell model induced with 6-OHDA neurotoxin.
  • Figure 11 is a diagram showing neuronal damage through trypan blue exclusion assay after administration of Humanin peptide to a Parkinson's disease cell model induced with 6-OHDA neurotoxin.
  • Figure 12 is a diagram showing the confirmation of neurons by administering Humanin peptide to a Parkinson's disease cell model induced by 6-OHDA or MPP+ neurotoxin in dopaminergic neurons derived from fetal midbrain undifferentiated neurons.
  • Figure 13 is a diagram showing the length of nerve cell protrusions by administering Humanin peptide to a Parkinson's disease cell model in which 6-OHDA or MPP+ neurotoxin was induced in dopaminergic neurons derived from fetal midbrain undifferentiated neurons.
  • Figure 14 is a diagram confirming the number of nerve cell projections by administering Humanin peptide to a Parkinson's disease cell model in which 6-OHDA or MPP+ neurotoxin was induced in dopaminergic neurons derived from fetal midbrain undifferentiated neurons.
  • Figure 15 shows that after intranasally injecting Humanin peptide (0.1 mg/kg, 5 mg/kg) for 8 days into a Parkinson's disease mouse model injected with the neurotoxin MPTP, the cerebrostriatal antioxidant enzyme NQO1 (Quinone-Oxidoreductase-1) ) This is a diagram showing the expression.
  • Figure 16 shows the cerebrostriatal antioxidant enzyme GSR (glutathione-disulfide reductase) after intranasal injection of Humanin peptide (0.1 mg/kg, 5 mg/kg) for 8 days in a Parkinson's disease mouse model injected with the neurotoxin MPTP. This is a diagram showing manifestation.
  • GSR glutathione-disulfide reductase
  • Figure 17 shows the level of cerebrostriatal antioxidant enzyme SOD1 (Superoxide dismutase-1) after intranasal injection of Humanin peptide (0.1 mg/kg, 5 mg/kg) for 8 days in a Parkinson's disease mouse model injected with the neurotoxin MPTP. This is a diagram showing manifestation.
  • SOD1 Superoxide dismutase-1
  • prevention may mean any act of suppressing or delaying the onset of a degenerative brain disease by administering the pharmaceutical composition for preventing or treating a degenerative brain disease according to the present invention to an individual.
  • treatment may refer to any act of administering the composition of the present invention to a subject suspected of developing a degenerative brain disease to improve or benefit the symptoms of the degenerative brain disease.
  • the term “improvement” may mean any action that reduces at least the degree of a parameter related to the condition being treated, such as a symptom.
  • alpha-synuclein ( ⁇ -syn) protein When alpha-synuclein ( ⁇ -syn) protein is abnormally formed, alpha-synuclein, the main causative gene for Parkinson's disease, binds and aggregates into a toxic oligomer and fibril form. When alpha-synuclein ( ⁇ -syn) is overproduced or in the presence of specific ligands, it forms oligomers and aggregates into mature fibrils.
  • the present invention provides a composition for preventing or treating degenerative brain diseases containing Humanin peptide as an active ingredient.
  • the pharmaceutical composition of the present invention may further include adjuvants in addition to the active ingredients.
  • adjuvants Any adjuvant known in the art may be used without limitation, but, for example, Freund's complete adjuvant or incomplete adjuvant may be further included to increase immunity.
  • composition according to the present invention can be prepared by incorporating the active ingredient into a pharmaceutically acceptable carrier.
  • pharmaceutically acceptable carriers include carriers, excipients, and diluents commonly used in the pharmaceutical field.
  • Pharmaceutically acceptable carriers that can be used in the pharmaceutical composition of the present invention include, but are not limited to, lactose, dextrose, sucrose, sorbitol, mannitol, xylitol, erythritol, maltitol, starch, gum acacia, alginate, gelatin, Examples include calcium phosphate, calcium silicate, cellulose, methyl cellulose, polyvinyl pyrrolidone, water, methylhydroxybenzoate, propylhydroxybenzoate, talc, magnesium stearate and mineral oil.
  • the pharmaceutical composition of the present invention can be formulated and used in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, or sterile injection solutions according to conventional methods. .
  • Solid preparations for oral administration include tablets, pills, powders, granules, capsules, etc., and such solid preparations contain the active ingredient plus at least one excipient, such as starch, calcium carbonate, sucrose, lactose, and gelatin. It can be prepared by mixing etc. Additionally, in addition to simple excipients, lubricants such as magnesium stearate and talc can also be used.
  • Liquid preparations for oral administration include suspensions, oral solutions, emulsions, and syrups.
  • Preparations for parenteral administration include sterile aqueous solutions, non-aqueous solutions, suspensions, emulsions, lyophilized preparations, and suppositories.
  • Non-aqueous solvents and suspensions include propylene glycol, polyethylene glycol, vegetable oil such as olive oil, and injectable ester such as ethyl oleate.
  • injectable ester such as ethyl oleate.
  • composition according to the present invention can be administered to an individual through various routes. All modes of administration are contemplated, for example, by oral, intravenous, intramuscular, subcutaneous, or intraperitoneal injection.
  • the pharmaceutical composition may be formulated into various oral or parenteral dosage forms.
  • Dosage forms for oral administration include, for example, tablets, pills, hard and soft capsules, solutions, suspensions, emulsifiers, syrups, granules, etc.
  • These dosage forms contain diluents (e.g. lactose, dextrose, water) in addition to the active ingredient.
  • diluents e.g. lactose, dextrose, water
  • lubricants e.g. silica, talc, stearic acid and its magnesium or calcium salts and/or polyethylene glycol.
  • the tablets may contain binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, and in some cases starch, agar, alginic acid. or disintegrants such as sodium salts thereof or effervescent mixtures and/or absorbents, colorants, flavoring and sweetening agents.
  • binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, and in some cases starch, agar, alginic acid. or disintegrants such as sodium salts thereof or effervescent mixtures and/or absorbents, colorants, flavoring and sweetening agents.
  • binders such as magnesium aluminum silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose and/or polyvinylpyrrolidine, and in some cases starch, agar,
  • representative formulations for parenteral administration are injectable formulations, and solvents for injectable formulations include water, Ringer's solution, isotonic saline solution, or suspension.
  • solvents for injectable formulations include water, Ringer's solution, isotonic saline solution, or suspension.
  • the sterile fixed oil of the injectable preparation can be used as a solvent or suspending medium, and any non-irritating fixed oil, including mono- and di-glycerides, can be used for this purpose.
  • the injectable preparation may use fatty acids such as oleic acid.
  • the humanin peptide may be represented by SEQ ID NO: 1.
  • the method of administering the Humanin peptide may be one or more of the following: nasal administration, oral administration, transdermal administration, subcutaneous administration, sublingual administration, intradermal administration, oral administration, topical administration, and ophthalmic administration. However, it is specifically a nasal administration.
  • the humanin peptide may include SEQ ID NO: 1.
  • the composition may inhibit damage to substantia nigra dopamine neurons, but is not limited thereto.
  • the composition may, but is not limited to, increase striatal dopamine neuron expression.
  • the composition may be used to restore nerve cell damage, but is not limited thereto.
  • the composition may increase the length or number of nerve cell projections, but is not limited thereto.
  • the composition increases the expression of antioxidant enzymes in the cerebrostriatum, but is not limited thereto.
  • the antioxidant enzymes include Quinone-Oxidoreductase-1 (NQO1), glutathione-disulfide reductase (GSR), and Superoxide dismutase-1 (SOD1), but are not limited thereto.
  • the degenerative brain disease includes Parkinson's disease (PD), Alzheimer's disease, progressive supranuclear palsy, multiple system atrophy, and olivary nucleus-pontine-cerebellar atrophy.
  • PD Parkinson's disease
  • Alzheimer's disease progressive supranuclear palsy, multiple system atrophy
  • olivary nucleus-pontine-cerebellar atrophy OPCA
  • Shy-Drager syndrome Striatonigral degeneration
  • Huntington's disease Huntington's disease
  • ALS Amyotrophic lateral sclerosis
  • Essential tremor essential tremor
  • Cortico-basal ganlionic degeneration Diffuse Lewy body disease
  • Parkinson-ALS-dementia complex of Guam Pick's disease ( It may be one or more selected from the group consisting of Pick's disease, but is not limited thereto.
  • Alpha-synuclein the main causative gene for Parkinson's disease, is a toxic oligomer that binds and aggregates when the alpha-synuclein protein is formed abnormally. , it converts into a fibril form, and overproduction of ⁇ -synuclein or the presence of a specific ligand forms oligomers and aggregates into mature fibrils.
  • Example 1-1 Mitochondrial-derived peptide Humanin peptide synthesis sequence
  • the mitochondria-derived peptide Humanin peptide of the present invention was synthesized in the following steps. One). Humanin peptide was weighed with 10 g of Fmoc-Ala-2-CTC resin (loading 0.3 mmol/g), added to the reaction column, and swollen with DCM for 30 minutes. 2). Fmoc was deprotected with 20% Piperidine/DMF, mixed for 10 minutes, washed with DMF, and the washing step was repeated. 3). 6 mmol Fmoc-Arg(Pbf)-OH, 6 mmol HOBT, 6 mmol HBTU, and 6 mmol DIEA were added to the resin and coupled for 40 min at room temperature. 4).
  • Steps 2) through 4) were repeated to increase the length of the peptide chain until all amino acids were sequentially bound to the chain. 6). After the last amino acid was attached to the chain, the peptide was deprotected, the resin was washed three times with MeOH, and the resin was dried. 7). Put the resin in a tube, add an appropriate amount of cleavage solution, incubate at 35 degrees for 2.5 hours, and add ether to precipitate the solution. 8) The peptide sample was air-dried and then freeze-dried to synthesize the Humanin peptide of the present invention.
  • the humanin peptide is included in SEQ ID NO: 1.
  • Example 1-2 Process of intranasal administration of Humanin peptide, a mitochondria-derived peptide
  • Humanin is a composition containing 24 amino acids, and the final concentration (0.1 mg/kg, 5 mg/kg) is obtained by adding RNase-free water to the dried powder. 40 ⁇ l of the solution was injected into the mouse, 20 ⁇ l each, into the left and right nostrils for 3 minutes using a micropipette. To help absorb the injected reagent, the mouse head was kept in a downward position for 3 minutes after injection.
  • the neurotoxin MPTP was administered intranasally once a day for a total of 8 days, starting 3 days before injection and 4 days after MPTP injection.
  • C57BL/6 male mice DBL Co., Ltd., Korea
  • weighing approximately 25 g were bred in the animal laboratory of the College of Life and Resources Sciences at Dong-A University. Water and feed were allowed to be consumed freely, and temperature (23 ⁇ 2°C), humidity (55 ⁇ 10%), and light/dark cycle (12 hours) were automatically controlled. All animals were acclimatized for 7 days before drug administration. All experiments were conducted in accordance with the approval of Dong-A University Animal Experiment Ethics Committee (DIACUC-Approval-20-25).
  • Animal model was created by intraperitoneally administering 20 mg/kg of MPTP hydrochloride (1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride, Sigma-Aldrich, USA) to experimental animals at 2-hour intervals four times a day. was prepared, and the control group was administered the same volume of sterile saline solution in the same manner.
  • MPTP hydrochloride 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride, Sigma-Aldrich, USA
  • mice An alpha-synuclein gene animal model was used as a genetically modified model for Parkinson's disease.
  • the C57BL/6-Tg(NSE-h ⁇ Syn)Korl model is a mouse that has been genetically modified to overexpress ⁇ -synuclein, the causative agent of Parkinson's disease, only in brain tissue.
  • Genetically modified mice were purchased from the Korea Food and Drug Safety Evaluation Institute (registration number 18-NIFDS-M-NE-014), and 12-month-old mice were used in the experiment.
  • Example 2-4 6-OHDA toxicity cell model using human neuroblastoma SH-SY5Y
  • a Parkinson's disease cell model was created by treating SH-SY5Y cells, a human neuroblastoma cell, with 6-OHDA (6-Hydroxydopamine hydrobromide, Sigma-Aldrich, USA) neurotoxin. 100 ⁇ M of 6-OHDA was treated for 24 hours, and cell damage was measured using the MTT Assay Kit (abcam, USA).
  • 6-OHDA 6-Hydroxydopamine hydrobromide
  • Example 2-5 MPP+, 6-OHDA toxicity cell model using primary midbrain dopaminergic neurons
  • Neurons were obtained by dissecting brain tissue from the cortex of mouse (C57BL6) embryos on day 13.5 (E13.5) of embryogenesis. To induce differentiation, embryonic cells were treated with 0.025% trypsin/EDTA and then attached to a glass coverslip coated with poly-L-ornithine (PLO, Sigma-Aldrich, USA).
  • Cell culture medium for neuronal differentiation is Neurobasal medium containing 50 U/ml penicillin and streptomycin, 1x B-27 supplement, 5% (vol/vol) FBS, 0.36% D-(+)-Glucose (wt/vol), and 0.25% Prepared by adding BSA (wt/vol). It was cultured in a 5% CO2 incubator for 9 days and then used in the experiment.
  • the humanin peptide of the present invention When the humanin peptide of the present invention is administered intranasally to the MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model, the time and bar for which the mouse model changes direction by raising and lowering the bar The ability to improve exercise was confirmed by measuring the total time to come down.
  • MPTP 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a prodrug of the neurotoxic MPP + , which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain. .
  • BBB blood brain barrier
  • Example 5 Confirmation of the amount of humanin peptide circulating in the body of normal patients and Parkinson's disease patients
  • Normal patients are those with no current or past clinical history of malignant tumors and no systemic diseases such as diabetes, high blood pressure, viral infections, or tuberculosis.
  • Example 6 Confirmation of inhibition of nerve cell damage by the Humanin peptide of the present invention.
  • Example 6-1 Confirmation of inhibition of nerve cell damage by the Humanin peptide of the present invention (in vivo)
  • Humanin peptide of the present invention inhibits nerve cell damage
  • Humanin peptide 0.1 mg/kg, 5 mg/kg
  • suppression of damage to substantia nigra dopamine neurons and expression of dopamine neurons in the cerebrostriatum were confirmed.
  • Example 6-2 Confirmation of inhibition of nerve cell damage by the Humanin peptide of the present invention (in vitro)
  • Humanin was applied to SH-SY5Y cells, a human neuroblastoma cell model, in a Parkinson's disease cell model induced by the neurotoxin 6-OHDA. 24 hours have passed since treatment at different peptide concentrations (0.1, 1, 10, 50 um).
  • the degree of nerve cell damage was analyzed through MTT assay and trypan blue exclusion assay at different humanin peptide concentrations (0.1, 1, 10, and 50 ⁇ m).
  • Example 8 Analysis of antioxidant enzyme expression in the Humanin peptide Parkinson's disease mouse model of the present invention
  • the Humanin peptide of the present invention was administered to a Parkinson's disease mouse model injected with the neurotoxin MPTP to express antioxidant enzymes NQO1, GSR, and SOD1 in the striatum. was analyzed.
  • Humanin peptide (0.1 mg/kg, 5 mg/kg) was injected intranasally for 8 days into a Parkinson's disease mouse model injected with the neurotoxin MPTP. As a result, Humanin peptide from the Parkinson's disease mouse model was administered intranasally. Upon administration, it was confirmed that the higher the concentration, the higher the expression of NQO1, GSR, and SOD1, confirming that the Humanin peptide of the present invention expresses antioxidant enzymes in the brain ( Figures 15, 16, and 17) .
  • the present invention provides a method for preventing and treating degenerative brain diseases comprising administering a pharmaceutically effective amount of the humanin to an individual.
  • the pharmaceutical composition of the present invention is administered in a therapeutically effective or pharmaceutically effective amount.
  • pharmaceutically effective amount means an amount sufficient to treat a disease with a reasonable benefit/risk ratio applicable to medical treatment, and the effective dose level is determined by the type and severity of the subject, age, sex, activity of the drug, and It can be determined based on factors including sensitivity, time of administration, route of administration and excretion rate, duration of treatment, concurrently used drugs, and other factors well known in the medical field.

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Abstract

L'objet de la présente invention est de fournir une composition pour la prévention ou le traitement de troubles neurodégénératifs, comprenant le peptide humanine utilisé comme principe actif. Après administration par voie nasale du peptide humanine selon la présente invention à un modèle de souris de la maladie de Parkinson, il a été confirmé que le peptide humanine a été efficacement délivré et distribué au cerveau. De plus, il a été confirmé que l'expression des neurones dopaminergiques s'est accru et que les lésions des cellules neuronales ont été supprimées. En outre, il a été confirmé que le peptide humanine supprime les lésions des cellules neuronales dans un modèle cellulaire de la maladie de Parkinson, étant ainsi efficace dans le traitement de la maladie de Parkinson, et, en conséquence, peut être utilisé dans des entreprises apparentées.
PCT/KR2022/018471 2022-10-12 2022-11-22 Composition pour la prévention ou le traitement de troubles neurodégénératifs, comprenant le peptide humanine utilisé comme principe actif WO2024080440A1 (fr)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7053053B2 (en) * 2001-06-15 2006-05-30 Takeda Chemical Industries, Ltd. Humanin-like peptide and use thereof
US20080125491A1 (en) * 2003-03-17 2008-05-29 Arena Pharmaceuticals, Inc. Human G Protein-Coupled Receptor and Modulators Thereof for the Treatment of Cell Death-Related Disorders
JP2012092048A (ja) * 2010-10-27 2012-05-17 Keio Gijuku 軽度認知障害の治療用医薬剤、初期認知症の治療用医薬剤、神経細胞の樹状突起形成促進剤、神経細胞のシナプス形成促進剤、検定方法およびスクリーニング方法
WO2013066374A2 (fr) * 2011-11-02 2013-05-10 Albert Einstein College Of Medicine Of Yeshiva University Protection par l'humanine des neurones dopaminergiques

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7053053B2 (en) * 2001-06-15 2006-05-30 Takeda Chemical Industries, Ltd. Humanin-like peptide and use thereof
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