CA2404237A1 - Methods of investigating, diagnosing, and treating amyloidosis - Google Patents
Methods of investigating, diagnosing, and treating amyloidosis Download PDFInfo
- Publication number
- CA2404237A1 CA2404237A1 CA002404237A CA2404237A CA2404237A1 CA 2404237 A1 CA2404237 A1 CA 2404237A1 CA 002404237 A CA002404237 A CA 002404237A CA 2404237 A CA2404237 A CA 2404237A CA 2404237 A1 CA2404237 A1 CA 2404237A1
- Authority
- CA
- Canada
- Prior art keywords
- transgenic animal
- amyloidosis
- test agent
- effective
- agent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Classifications
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/39—Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
-
- 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
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/1703—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates
- A61K38/1709—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans from vertebrates from mammals
-
- 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
Abstract
The present invention provides a therapeutic method for removing amyloid fibrils from a patient. The present invention also provides a transgenic animal that develops systemic AA amyloidosis within three weeks for use as a tool to investigate AA amyloidosis and to evaluate agents that may be potentially useful in preventing and treating amyloid-related disorders. Further, the present invention provides diagnostic assays for monitoring immunoglobulin light chain fibrillogenesis in real-time and for identificati on of the chemical nature of the protein in amyloid deposits which enables the determination of the type of amyloidosis for therapeutic and prognostic purposes.
Claims (15)
1. A method of removing amyloid deposits from a patient comprising administering to the patient amyloid fibril in an effective amount to generate an immune response that will promote the removal of in vivo amyloid fibrils from the patient.
2. The method of claim 1, wherein the amyloid fibril comprises an amyloid light chain polypeptide or whole light chain.
3. A vaccine or pharmaceutical composition comprising an amyloid fibril and a carrier.
4. A transgenic non-human animal that develops extensive AA amyloid deposits after administration of amyloid enhancing factor (AEF).
5. The transgenic non-human animal of claim 4, wherein the animal is a mouse.
6. A method of increasing the rate of development of amyloid deposits in a transgenic animal carrying an IL-6 gene under the control of a promoter or enhancer comprising administering to the animal an effective amount of amyloid enhancing factor (AEF), wherein the increase in rate of development of amyloid deposits is relative to a transgenic animal not administered with AEF.
7. The method of claim 6, wherein the transgenic animal is a transgenic mouse.
8. The method of claim 7, wherein the transgenic mouse develops amyloid deposits after receiving AEF.
9. A method of identifying an agent effective in preventing amyloidosis comprising administering a test agent to a young transgenic animal carrying an IL-6 gene under the control of a promoter or enhancer, determining the life span of the transgenic animal, and comparing its life span to that of a control young transgenic animal, wherein a longer life span of the transgenic animal administered with a test agent indicates that the test agent is effective in preventing amyloidosis.
10. A method of identifying an agent effective in preventing amyloidosis comprising administering a test agent and AEF to a young transgenic animal carrying an IL-6 gene under the control of a promoter or enhancer, determining the life span of the transgenic animal, and comparing its life span to that of a control young transgenic animal, wherein a longer life span of the transgenic animal administered with the test agent indicates that the test agent is effective in preventing amyloidosis.
11. The method of claim 9 or 10, wherein the transgenic animal is a mouse.
12. A method of identifying an agent effective in treating amyloidosis comprising administering a test agent to a transgenic animal carrying an IL-6 gene under the control of a promoter or an enhancer and having amyloid deposits in its body, determining the life span of the transgeruc animal, and comparing its life span to that of a control transgenic animal, wherein a longer life span of the transgenic animal administered with the test agent indicates that the test agent is effective in treating amyloidosis.
13. A method of identifying an agent effective in treating amyloidosis comprising administering AEF to a young transgenic animal carrying an IL-6 gene under the control of a promoter or enhancer, administering a test agent after development of amyloidosis, determining the life span of the transgenic animal, and comparing its life span to that of a control young transgenic animal, wherein a longer life span of the transgenic animal administered with the test agent indicates that the test agent is effective in treating amyloidosis.
14. The method of claim 12 or 13, wherein the transgenic animal is a mouse.
15. The method of any one of claims 9, 10, 12, or 13, wherein the IL-6 gene is a human IL-6 gene.
17. A method of identifying an agent effective in preventing amyloidosis comprising administering a test agent to a young transgenic animal carrying an IL-6 gene under the control of a promoter or enhancer, and detecting development of amyloid deposits by radiographic imaging of the transgenic animal, wherein an absence of amyloid deposits indicates that the test agent is effective in preventing amyloidosis.
18. A method of identifying an agent effective in preventing amyloidosis comprising administering a test agent and AEF to a young transgenic animal carrying an IL-6 gene under the control of a promoter or enhancer, and detecting development of amyloid deposits by radiographic imaging of the transgenic animal, wherein an absence of amyloid deposits indicates that the test agent is effective in preventing amyloidosis.
19. The method of claim 17 or 18, wherein the transgenic animal is a mouse.
20. The method of claim 17 or 18, wherein radiographic imaging is performed via MRI, CT, or SPELT scan.
21. A method of identifying an agent effective in treating amyloidosis comprising administering a test agent to a transgenic animal carrying an IL-6 gene under the control of a promoter or enhancer and having amyloid deposits in its body, detecting amyloid deposits by radiographic imaging of the transgenic animal, wherein a decrease or a constant level of amyloid deposits in the transgenic animal as compared to a control animal indicates that the test agent is effective in treating amyloidosis.
22. A method of identifying an agent, effective in treating amyloidosis comprising administering AEF to a young transgenic animal carrying an IL-6 gene under the control of a promoter or enhancer, administering a test agent after development of amyloidosis, and detecting development of amyloid deposits by radiographic imaging of the transgenic animal, wherein a decrease or constant level of amyloid deposits in the transgenic animal as compared to a control animal indicates that the test agent is effective in treating amyloidosis.
23. The method of claim 21 or 22, wherein the transgenic animal is a mouse.
24. The method of claim 21 or 22, wherein radiographic imaging is performed via MRI, CT, or SPELT scan 25. The method of any one of claims 17, 18, 21, or 22, wherein the IL-6 gene is a human IL-6 gene.
26. The method of any one of claims 9, 10, 12, 13, 17, 18, 21, or 22, wherein the promoter is a metallothionein-I promoter.
27. The method of any one of claims 9, 10, 12, 13, 17, 18, 21, or 22, wherein the enhancer is an Eµ, enhancer.
28: A method of identifying an agent that inhibits fibrillogenesis of a polypeptide comprising:
a) incubating a test agent with a polypeptide known to form fibrils and ThT;
and b) measuring the fluorescence intensity as a function of time to determine whether the agent inhibits fibrillogenesis of the polypeptide.
29. A method of determining whether a compound is fibrillogenic comprising:
a) incubating the compound with ThT; and b) measuring fluorescence intensity as a function of time of to determine whether the compound is fibrillogenic.
30. A method of identifying the chemical nature of proteins in amyloid deposits comprising:
a) extracting the proteins from ultra-thin sections of formalin fixed, paraffin-embedded tissue biopsy specimens;
b) isolating the proteins; and c) determining the amino acid sequence of each of the proteins.
31. The method of any one of claims, 9, 10, 13, 17, 18, or 22, wherein the transgenic animal is six week old.
32. The method of any one of claims 9, 10, 12, 13, 17, 18, 21, or 22, wherein the amyloidosis is AA amyloidosis.
17. A method of identifying an agent effective in preventing amyloidosis comprising administering a test agent to a young transgenic animal carrying an IL-6 gene under the control of a promoter or enhancer, and detecting development of amyloid deposits by radiographic imaging of the transgenic animal, wherein an absence of amyloid deposits indicates that the test agent is effective in preventing amyloidosis.
18. A method of identifying an agent effective in preventing amyloidosis comprising administering a test agent and AEF to a young transgenic animal carrying an IL-6 gene under the control of a promoter or enhancer, and detecting development of amyloid deposits by radiographic imaging of the transgenic animal, wherein an absence of amyloid deposits indicates that the test agent is effective in preventing amyloidosis.
19. The method of claim 17 or 18, wherein the transgenic animal is a mouse.
20. The method of claim 17 or 18, wherein radiographic imaging is performed via MRI, CT, or SPELT scan.
21. A method of identifying an agent effective in treating amyloidosis comprising administering a test agent to a transgenic animal carrying an IL-6 gene under the control of a promoter or enhancer and having amyloid deposits in its body, detecting amyloid deposits by radiographic imaging of the transgenic animal, wherein a decrease or a constant level of amyloid deposits in the transgenic animal as compared to a control animal indicates that the test agent is effective in treating amyloidosis.
22. A method of identifying an agent, effective in treating amyloidosis comprising administering AEF to a young transgenic animal carrying an IL-6 gene under the control of a promoter or enhancer, administering a test agent after development of amyloidosis, and detecting development of amyloid deposits by radiographic imaging of the transgenic animal, wherein a decrease or constant level of amyloid deposits in the transgenic animal as compared to a control animal indicates that the test agent is effective in treating amyloidosis.
23. The method of claim 21 or 22, wherein the transgenic animal is a mouse.
24. The method of claim 21 or 22, wherein radiographic imaging is performed via MRI, CT, or SPELT scan 25. The method of any one of claims 17, 18, 21, or 22, wherein the IL-6 gene is a human IL-6 gene.
26. The method of any one of claims 9, 10, 12, 13, 17, 18, 21, or 22, wherein the promoter is a metallothionein-I promoter.
27. The method of any one of claims 9, 10, 12, 13, 17, 18, 21, or 22, wherein the enhancer is an Eµ, enhancer.
28: A method of identifying an agent that inhibits fibrillogenesis of a polypeptide comprising:
a) incubating a test agent with a polypeptide known to form fibrils and ThT;
and b) measuring the fluorescence intensity as a function of time to determine whether the agent inhibits fibrillogenesis of the polypeptide.
29. A method of determining whether a compound is fibrillogenic comprising:
a) incubating the compound with ThT; and b) measuring fluorescence intensity as a function of time of to determine whether the compound is fibrillogenic.
30. A method of identifying the chemical nature of proteins in amyloid deposits comprising:
a) extracting the proteins from ultra-thin sections of formalin fixed, paraffin-embedded tissue biopsy specimens;
b) isolating the proteins; and c) determining the amino acid sequence of each of the proteins.
31. The method of any one of claims, 9, 10, 13, 17, 18, or 22, wherein the transgenic animal is six week old.
32. The method of any one of claims 9, 10, 12, 13, 17, 18, 21, or 22, wherein the amyloidosis is AA amyloidosis.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US19468400P | 2000-04-05 | 2000-04-05 | |
| US60/194,684 | 2000-04-05 | ||
| PCT/US2001/011043 WO2001077167A2 (en) | 2000-04-05 | 2001-04-05 | Methods of investigating, diagnosing, and treating amyloidosis |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2404237A1 true CA2404237A1 (en) | 2001-10-18 |
| CA2404237C CA2404237C (en) | 2010-01-26 |
Family
ID=22718526
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2404237A Expired - Fee Related CA2404237C (en) | 2000-04-05 | 2001-04-05 | Methods of investigating, diagnosing, and treating amyloidosis |
Country Status (5)
| Country | Link |
|---|---|
| US (1) | US7485616B2 (en) |
| EP (1) | EP1353944A2 (en) |
| AU (1) | AU2001253158A1 (en) |
| CA (1) | CA2404237C (en) |
| WO (1) | WO2001077167A2 (en) |
Families Citing this family (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6905686B1 (en) | 1997-12-02 | 2005-06-14 | Neuralab Limited | Active immunization for treatment of alzheimer's disease |
| TWI239847B (en) | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
| US6750324B1 (en) | 1997-12-02 | 2004-06-15 | Neuralab Limited | Humanized and chimeric N-terminal amyloid beta-antibodies |
| US20080050367A1 (en) | 1998-04-07 | 2008-02-28 | Guriq Basi | Humanized antibodies that recognize beta amyloid peptide |
| US6761888B1 (en) | 2000-05-26 | 2004-07-13 | Neuralab Limited | Passive immunization treatment of Alzheimer's disease |
| US6787523B1 (en) | 1997-12-02 | 2004-09-07 | Neuralab Limited | Prevention and treatment of amyloidogenic disease |
| US7964192B1 (en) | 1997-12-02 | 2011-06-21 | Janssen Alzheimer Immunotherapy | Prevention and treatment of amyloidgenic disease |
| US7790856B2 (en) | 1998-04-07 | 2010-09-07 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize beta amyloid peptide |
| US20030147882A1 (en) | 1998-05-21 | 2003-08-07 | Alan Solomon | Methods for amyloid removal using anti-amyloid antibodies |
| US6787637B1 (en) | 1999-05-28 | 2004-09-07 | Neuralab Limited | N-Terminal amyloid-β antibodies |
| UA81216C2 (en) | 1999-06-01 | 2007-12-25 | Prevention and treatment of amyloid disease | |
| CA2404237C (en) * | 2000-04-05 | 2010-01-26 | University Of Tennessee Research Corporation | Methods of investigating, diagnosing, and treating amyloidosis |
| US7700751B2 (en) | 2000-12-06 | 2010-04-20 | Janssen Alzheimer Immunotherapy | Humanized antibodies that recognize β-amyloid peptide |
| MY139983A (en) | 2002-03-12 | 2009-11-30 | Janssen Alzheimer Immunotherap | Humanized antibodies that recognize beta amyloid peptide |
| US20040146512A1 (en) * | 2002-10-09 | 2004-07-29 | Arnon Rosenthal | Methods of treating Alzheimer's disease using antibodies directed against amyloid beta peptide and compositions thereof |
| TWI306458B (en) | 2003-05-30 | 2009-02-21 | Elan Pharma Int Ltd | Humanized antibodies that recognize beta amyloid peptide |
| WO2005059100A2 (en) * | 2003-12-12 | 2005-06-30 | New York University | Methods and compositions relating to cystatin c |
| AP2007003890A0 (en) * | 2004-07-30 | 2007-02-28 | Rinat Neuroscience Corp | Antibodies directed against amy-loid-beta peptide and methods using same |
| PE20061329A1 (en) | 2004-12-15 | 2006-12-08 | Neuralab Ltd | HUMANIZED AB ANTIBODIES TO IMPROVE COGNITION |
| MY148086A (en) * | 2005-04-29 | 2013-02-28 | Rinat Neuroscience Corp | Antibodies directed against amyloid-beta peptide and methods using same |
| US20090175894A1 (en) * | 2005-10-17 | 2009-07-09 | Golde Todd E | Methods and materials for producing a generic anti-amyloid immune response in mammals |
| US8784810B2 (en) | 2006-04-18 | 2014-07-22 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases |
| US8003097B2 (en) | 2007-04-18 | 2011-08-23 | Janssen Alzheimer Immunotherapy | Treatment of cerebral amyloid angiopathy |
| SI2182983T1 (en) | 2007-07-27 | 2014-09-30 | Janssen Alzheimer Immunotherapy | Treatment of amyloidogenic diseases with humanised anti-abeta antibodies |
| JO3076B1 (en) | 2007-10-17 | 2017-03-15 | Janssen Alzheimer Immunotherap | Immunotherapy regimes dependent on apoe status |
| HUE025560T2 (en) | 2007-12-28 | 2016-03-29 | Prothena Biosciences Ltd | Treatment and prophylaxis of amyloidosis |
| FI20085340L (en) * | 2008-04-22 | 2009-10-23 | Medixine Oy | Health screening and a method for implementing the health screening |
| US9067981B1 (en) | 2008-10-30 | 2015-06-30 | Janssen Sciences Ireland Uc | Hybrid amyloid-beta antibodies |
| US9683017B2 (en) | 2014-07-17 | 2017-06-20 | University Tennessee Research Foundation | Inhibitory peptides of viral infection |
| US10213506B2 (en) | 2014-08-26 | 2019-02-26 | University Of Tennessee Research Foundation | Targeting immunotherapy for amyloidosis |
| US10464999B2 (en) | 2015-01-28 | 2019-11-05 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
| US9879080B2 (en) | 2015-01-28 | 2018-01-30 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
| US10633433B2 (en) | 2015-01-28 | 2020-04-28 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
| WO2017184973A1 (en) * | 2016-04-22 | 2017-10-26 | University Of Tennessee Research Foundation | Identifying amyloidogenic proteins & amyloidogenic risk |
| JP7357609B2 (en) | 2017-10-06 | 2023-10-06 | ノボ ノルディスク エー／エス | anti-transthyretin antibody |
| JOP20200132A1 (en) | 2017-11-29 | 2022-10-30 | Prothena Biosciences Ltd [Ie/Ie] | Lyophilized formulation of a monoclonal antibody against transthyretin |
| WO2021168156A1 (en) * | 2020-02-20 | 2021-08-26 | Prothena Biosciences Limited | Monitoring transthyretin amyloidosis |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3521684A1 (en) * | 1985-06-18 | 1986-12-18 | Dr. Müller-Lierheim KG, Biologische Laboratorien, 8033 Planegg | METHOD FOR COATING POLYMERS |
| EP0526511B1 (en) | 1990-04-27 | 1997-05-28 | MCMICHAEL, John | Method and composition for treatment of central nervous systems disease states associated with abnormal amyloid beta protein |
| JP2988635B2 (en) * | 1990-09-18 | 1999-12-13 | 塩野義製薬株式会社 | Monoclonal antibody against human IgE |
| AU4382193A (en) * | 1992-05-19 | 1993-12-13 | Xoma Corporation | BPI-immunoglobulin fusion proteins |
| US5750106A (en) * | 1993-01-28 | 1998-05-12 | Novartis Ag | Human monoclonal antibodies to cytomegalovirus |
| US5744368A (en) * | 1993-11-04 | 1998-04-28 | Research Foundation Of State University Of New York | Methods for the detection of soluble amyloid β-protein (βAP) or soluble transthyretin (TTR) |
| JP3064013B2 (en) | 1994-05-25 | 2000-07-12 | ジョン マクマイケル， | Methods and materials for the treatment of plaque forming disorders |
| US5786180A (en) * | 1995-02-14 | 1998-07-28 | Bayer Corporation | Monoclonal antibody 369.2B specific for β A4 peptide |
| TWI239847B (en) * | 1997-12-02 | 2005-09-21 | Elan Pharm Inc | N-terminal fragment of Abeta peptide and an adjuvant for preventing and treating amyloidogenic disease |
| US6913745B1 (en) * | 1997-12-02 | 2005-07-05 | Neuralab Limited | Passive immunization of Alzheimer's disease |
| NZ507727A (en) | 1998-05-21 | 2003-11-28 | Univ Tennessee Res Foundation | Methods for amyloid removal using anti-amloid antibodies |
| UA81216C2 (en) * | 1999-06-01 | 2007-12-25 | Prevention and treatment of amyloid disease | |
| CA2404237C (en) * | 2000-04-05 | 2010-01-26 | University Of Tennessee Research Corporation | Methods of investigating, diagnosing, and treating amyloidosis |
-
2001
- 2001-04-05 CA CA2404237A patent/CA2404237C/en not_active Expired - Fee Related
- 2001-04-05 US US09/825,872 patent/US7485616B2/en not_active Expired - Fee Related
- 2001-04-05 EP EP01926636A patent/EP1353944A2/en not_active Withdrawn
- 2001-04-05 WO PCT/US2001/011043 patent/WO2001077167A2/en active Application Filing
- 2001-04-05 AU AU2001253158A patent/AU2001253158A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| US20020019335A1 (en) | 2002-02-14 |
| WO2001077167A2 (en) | 2001-10-18 |
| EP1353944A2 (en) | 2003-10-22 |
| AU2001253158A1 (en) | 2001-10-23 |
| US7485616B2 (en) | 2009-02-03 |
| CA2404237C (en) | 2010-01-26 |
| WO2001077167A3 (en) | 2003-08-28 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |