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Methods and compositions to detect the level of lysosomal exocytosis activity and methods of use

a technology of exocytosis activity and detection method, applied in the field of molecular biology, cancer and alzheimer's disease therapeutics and diagnostics, can solve the problems of lack of reliable prognostic and diagnostic methods for managing disease states, and achieve the effect of low lysosomal sialidase activity

Active Publication Date: 2014-12-25
ST JUDE CHILDRENS RES HOSPITAL INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, reliable prognostic and diagnostic methods are lacking for managing disease states.
Thus, due to the lack of suitable diagnostic methods only a tentative diagnosis can be provided.

Method used

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  • Methods and compositions to detect the level of lysosomal exocytosis activity and methods of use
  • Methods and compositions to detect the level of lysosomal exocytosis activity and methods of use
  • Methods and compositions to detect the level of lysosomal exocytosis activity and methods of use

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Experimental program
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Effect test

embodiment 1

11. The method of embodiment 1, wherein the one or more values representing lysosomal sialidase activity comprise the level of MUC-1 protein.

12. The method of any one of embodiments 1-11, wherein the cancer comprises rhabdomyosarcoma, breast cancer, colon cancer, pancreatic cancer, acute lymphoblastic leukemia or Ewing's sarcoma.

13. A method of diagnosing dementia associated with Alzheimer's disease in a subject, the method comprising:[0178]a) providing a subject lysosomal exocytosis activity profile of a sample of cerebrospinal fluid from said subject;[0179]b) providing a reference lysosomal exocytosis activity profile of a control sample of cerebrospinal fluid, wherein the subject lysosomal exocytosis activity profile and the corresponding reference lysosomal exocytosis activity profile comprise one or more values representing lysosomal exocytosis activity; and,[0180]c) comparing said subject and said reference lysosomal exocytosis activity profiles, wherein said subject is diagno...

embodiment 28

29. The method of embodiment 28, wherein the NEU1 polypeptide and PPCA polypeptide are administered separately or simultaneously.

embodiment 29

30. The method of embodiment 29, wherein administration of the NEU1 polypeptide comprises administration of a viral vector comprising a nucleotide sequence having at least 85% sequence identity to SEQ ID NO: 1.

31. A method of generating a lysosomal sialidase activity profile comprising:[0183](a) obtaining a sample from a tumor from a subject; and,[0184](b) assaying for the level of LAMP-1 protein or the level of LAMP-1 sialylation.

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Abstract

Methods are provided for the prognosis, diagnosis and treatment of various pathological states, including cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. The methods provided herein are based on the discovery that various proteins with a high level of sialylation are shown herein to be associated with disease states, such as, cancer, chemotherapy resistance and dementia associated with Alzheimer's disease. Such methods provide a lysosomal exocytosis activity profile comprising one or more values representing lysosomal exocytosis activity. Also provided herein, is the discovery that low lysosomal sialidase activity is associated with various pathological states. Thus, the methods also provide a lysosomal sialidase activity profile, comprising one or more values representing lysosomal sialidase activity. A lysosomal sialidase activity profile is one example of a lysosomal exocytosis activity profile. As such, the level of lysosomal exocytosis activity and / or lysosomal sialidase activity is predictive of a diagnosis and / or prognosis of cancer, chemotherapy resistance or dementia associated with Alzheimer's disease.

Description

FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT[0001]This invention was made with Federal Government support under GM060950 awarded by the National Institutes of Health. The United States Government has certain rights in the invention. This invention was also supported by the American Lebanese Syrian Associated Charities (ALSAC) of St. Jude Children's Research Hospital.FIELD OF THE INVENTION[0002]The present invention relates to the field of molecular biology, cancer and Alzheimer's disease therapeutics and diagnostics.REFERENCE TO A SEQUENCE LISTING SUBMITTED AS A TEXT FILE VIA EFS-WEB[0003]The official copy of the sequence listing is submitted concurrently with the specification as a text file via EFS-Web, in compliance with the American Standard Code for Information Interchange (ASCII), with a file name of 423475SEQLIST.txt, a creation date of Aug. 22, 2012, and a size of 13 KB. The sequence listing filed via EFS-Web is part of the specification and is hereby incorporated in its enti...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/34A61K38/48G06F19/00A61K38/47
CPCG01N33/57484G01N2800/56G01N2333/924A61K38/4813C12Y302/01018A61K38/47A61K38/48A61P25/28A61P35/00G16H20/40Y02A90/10G01N2800/2821G16H20/00C07B59/005C12N15/86C12N2320/30C12Y304/16005C12N2710/10031C12N2740/10041C12N2750/14141C12N15/11C12N9/2402C12N9/485C12N15/00C12N15/63C12Q1/34G01N33/573G01N33/57496
Inventor ANNUNZIATA, IDAD'AZZO, ALESSANDRAWHITE-GILBERTSON, SHAI
Owner ST JUDE CHILDRENS RES HOSPITAL INC
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