Search

EP-4737902-A1 - COMPOSITION FOR DIAGNOSING PARKINSON?S DISEASE AND METHOD FOR DIAGNOSING PARKINSON?S DISEASE BY USING SAME

EP4737902A1EP 4737902 A1EP4737902 A1EP 4737902A1EP-4737902-A1

Abstract

The present invention relates to a composition for diagnosing Parkinson's disease, comprising an agent for detecting a protein consisting of a combination of GLUT3 and any one or more selected from the group consisting of USP14, α-synuclein, and AIMP2, or a gene encoding the protein. The composition for diagnosing Parkinson's disease and a diagnostic kit comprising the composition, of the present invention, can be used to perform detection or diagnosis by distinguishing Parkinson's disease patient groups through a simple blood test. Furthermore, by primarily applying same to patients showing prodromal symptoms of Parkinson's disease, such as olfactory dysfunction, sleep disorders, and constipation, the composition and the diagnostic kit can be used as a preliminary test to determine whether to perform neurological examinations and brain imaging tests at large hospitals. Also, the composition and the diagnostic kit can be used as a means for quantifying the effect of treating Parkinson's disease.

Inventors

  • LEE, YUNJONG
  • LEE, NAE-EUNG
  • SHIN, JEONG YONG
  • KIM, HEEJEONG
  • CHO, SEOK HYUN
  • KIM, HEE TAE

Assignees

  • Ninebiowear Co., Ltd.

Dates

Publication Date
20260506
Application Date
20240627

Claims (13)

  1. A composition for diagnosing Parkinson's disease, further comprising an agent for detecting at least one protein selected from the group consisting of GLUT3 (glucose transporter 3), USP14 (ubiquitin-specific protease 14), α-synuclein, and AIMP2 (aminoacyl-tRNA synthetase complex interacting multifunctional protein-2), an aggregate thereof, or a gene encoding same.
  2. The composition for diagnosing Parkinson's disease, comprising an agent for detecting a GLUT3 protein, an aggregate thereof, or a gene encoding same.
  3. The composition of claim 2, further comprising an agent for detecting at least one protein selected from the group consisting of USP14, α-synuclein, and AIMP2, an aggregate thereof, or a gene encoding same.
  4. The composition of claim 1, wherein the protein is a protein present in a blood sample isolated from a human.
  5. The composition of claim 1, wherein the agent for detecting the protein is at least one selected from the group consisting of an antibody, an aptamer, a ligand, a peptide nucleic acid (PNA), and an oligopeptide.
  6. The composition of claim 1, wherein the agent for detecting the gene is at least one selected from the group consisting of primers, probes, and antisense nucleotides.
  7. A kit for diagnosing Parkinson's disease, comprising the composition of any one of claims 1 to 6.
  8. A method for providing information for diagnosing Parkinson's disease, the method comprising the steps of: (a) measuring an expression level of GLUT3 protein, an aggregate thereof, or a gene encoding same in a blood sample isolated from a human; and (b) providing information that the likelihood of Parkinson's disease is high when the expression level is increased compared to a normal blood control sample.
  9. The method of claim 8, wherein step (a) includes the following step (a-1) and step (b) includes the following step (b-1): (a-1) measuring an expression level of a combination of GLUT3 and at least one selected from the group consisting of USP14, α-synuclein, and AIMP2, an aggregate thereof, or a gene encoding same in a blood sample isolated from a human, (b-1) providing information that the likelihood of Parkinson's disease is high when the expression level of a combination of GLUT3 and at least one selected from the group consisting of USP14, α-synuclein, and AIMP2, an aggregate thereof, or a gene encoding same in a blood sample isolated from a human are increased, compared to a normal blood control sample.
  10. The method of claim 8, wherein the step of measuring protein levels is performed using at least one agent selected from the group consisting of an antibody, an aptamer, a ligand, a peptide nucleic acid (PNA), and an oligopeptide.
  11. The method of claim 8, wherein the step of measuring gene expression levels is performed using at least one agent selected from the group consisting of primers, probes, and antisense nucleotides.
  12. A method for screening a therapeutic agent for Parkinson's disease, the method comprising the steps of: a) administering a drug candidate to a Parkinson's disease animal model in which the expression level of GLUT3 protein in blood, aggregates thereof, or a gene encoding the same is increased; b) collecting blood from the animal model and measuring the expression level of the protein or mRNA in the collected blood after step a); and c) determining the drug candidate as a therapeutic agent for Parkinson's disease when the expression level of GLUT3 protein, an aggregate thereof, or a gene encoding same in the collected blood shows a significant decrease due to administration of the drug candidate.
  13. The method of claim 12, wherein step a) includes the following step a-1) and step c) includes the following step c-1): a-1) administering a drug candidate to a Parkinson's disease animal model in which the expression level of a combination of GLUT3 and at least one protein selected from the group consisting of USP14, α-synuclein, and AIMP2, an aggregate thereof, or a gene encoding same in blood is increased; and c-1) determining the drug candidate as a therapeutic agent for Parkinson's disease when the expression level in the collected blood of GLUT3, and at least one protein selected from the group consisting of USP14, α-synuclein, and AIMP2, an aggregate thereof, or a gene encoding same, shows a significant decrease due to administration of the drug candidate.

Description

Technical Field The present disclosure was carried out with the support of the Ministry of Science and ICT of the Republic of Korea under Project No. 2021M3H4A4079521, wherein the research management agency is the National Research Foundation of Korea, the project title is "Development of Nanomaterials Technology," the research subject is "Development of Isothermal Amplification Electrochemical Molecular and Digital Fluorescence Imaging Immunodiagnostic Device," the supervising institution is Sungkyunkwan University, and the research period is from February 1, 2022 to January 31, 2023. The present disclosure was carried out with the support of the Ministry of Health and Welfare of the Republic of Korea under Project No. HU22C0143000022, wherein the research management agency is the Korea Health Industry Development Institute, the project title is "Dementia Overcoming Research and Development Project (Ministry of Health and Welfare)," the research subject is "Elucidation of the Pathogenesis and Lesion Propagation Brain Map of Lewy Body Dementia Based on the Alpha-Synuclein Aggregation/Propagation Promoting System Targeting AIMP2," the supervising institution is the Sungkyunkwan University Research & Business Foundation, and the research period is from April 1, 2022 to December 28, 2022. The present application claims the benefit of and priority to Korean Patent Application No. 10-2023-0083059, filed with the Korean Intellectual Property Office on June 27, 2023, the disclosure of which is incorporated herein by reference. The present disclosure relates to a composition for diagnosing Parkinson's disease through detection of expression level of at least one protein selected from the group consisting of GLUT3, USP14, α-synuclein, and AIMP2 in blood, or a gene coding therefor. Background Art Parkinson's disease is a neurodegenerative disorder, in which dopaminergic neurons of the substantia nigra located in the midbrain are destroyed, thereby causing movement disorders. Patients with Parkinson's disease exhibit not only motor symptoms but also non-motor symptoms such as olfactory dysfunction, sleep disorders, depression, mania, and cognitive impairment. In modern society, which is rapidly entering an aging era, the number of patients with Parkinson's disease is also rapidly increasing. According to the disease statistics data of the National Health Insurance Service, the number of Parkinson's disease patients in Korea increased approximately 2.5-fold, from 39,265 in 2004 to 96,499 in 2016. Diagnosis of Parkinson's disease relies heavily on quantitative scoring of motor/non-motor symptoms associated with Parkinson's disease based on the Unified Parkinson's Disease Rating Scale(UPDRS) by specialists. However, it has been reported that the misdiagnosis rate reaches as high as 25% in the early stage of Parkinson's disease (Thomas G. Beach et al., 2018). Although the loss of dopaminergic neurons can be diagnosed early by capturing DaTscan brain imaging of the axons of dopaminergic neurons, accessibility to patients is limited since such diagnosis can only be performed in large hospitals equipped with expensive equipment. For accurate and accessible diagnosis of Parkinson's disease, it is important to develop molecular diagnostic markers and portable diagnostic devices utilizing same. Molecular diagnostic markers can be used not only for diagnosis of the disease but also for quantification of symptom alleviation in clinical trials and prediction of treatment prognosis, thereby highlighting the need for research in this field. Throughout the specification, numerous papers and patent documents are referred to and cited. The disclosure of the cited papers and patent documents are incorporated herein in their entirety by reference, thereby clarifying the level of ordinary skill in the art to which the present disclosure pertains and enabling a clearer understanding of the present disclosure. Disclosure of Invention Technical Problem Leading to the present disclosure, intensive and thorough research conducted by the present inventors, with the aim of developing a diagnostic method that is capable of determining the possibility of onset of Parkinson's disease and enabling early diagnosis and which allows simple diagnosis of Parkinson's disease in a minimally invasive manner, resulted in the finding that early diagnosis of Parkinson's disease is possible through detection of the expression levels of GLUT3 and at least one protein selected from the group consisting of USP14, α-synuclein, and AIMP2 in blood. Accordingly, an aspect of the present disclosure is to provide a composition for diagnosing Parkinson's disease. Another aspect of the present disclosure is to provide a kit for diagnosing Parkinson's disease. Still another aspect of the present disclosure is to provide a method for providing information for diagnosing Parkinson's disease. A further aspect of the present disclosure is to provide a method for screening a th