GR20110100262A - Hybrid gene peptidomimetic vaccine for immunological response of patients having polyq diseases. - Google Patents
Hybrid gene peptidomimetic vaccine for immunological response of patients having polyq diseases.Info
- Publication number
- GR20110100262A GR20110100262A GR20110100262A GR20110100262A GR20110100262A GR 20110100262 A GR20110100262 A GR 20110100262A GR 20110100262 A GR20110100262 A GR 20110100262A GR 20110100262 A GR20110100262 A GR 20110100262A GR 20110100262 A GR20110100262 A GR 20110100262A
- Authority
- GR
- Greece
- Prior art keywords
- spinocerebellar ataxia
- ataxia type
- germ cells
- sirna
- mesenchymatic
- Prior art date
Links
- 108090000623 proteins and genes Proteins 0.000 title abstract 10
- 229960005486 vaccine Drugs 0.000 title abstract 5
- 201000010099 disease Diseases 0.000 title abstract 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract 4
- 230000028993 immune response Effects 0.000 title abstract 2
- 239000000816 peptidomimetic Substances 0.000 title 1
- 108010040003 polyglutamine Proteins 0.000 abstract 8
- 210000004602 germ cell Anatomy 0.000 abstract 6
- 108020004459 Small interfering RNA Proteins 0.000 abstract 5
- 230000000324 neuroprotective effect Effects 0.000 abstract 5
- 229920000155 polyglutamine Polymers 0.000 abstract 5
- 210000004556 brain Anatomy 0.000 abstract 4
- 238000000034 method Methods 0.000 abstract 4
- 239000000203 mixture Substances 0.000 abstract 4
- 102000004169 proteins and genes Human genes 0.000 abstract 4
- 208000023105 Huntington disease Diseases 0.000 abstract 3
- 208000002569 Machado-Joseph Disease Diseases 0.000 abstract 3
- 208000009415 Spinocerebellar Ataxias Diseases 0.000 abstract 3
- 208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 abstract 3
- 108090000765 processed proteins & peptides Proteins 0.000 abstract 3
- 201000003624 spinocerebellar ataxia type 1 Diseases 0.000 abstract 3
- 102000007372 Ataxin-1 Human genes 0.000 abstract 2
- 108010032963 Ataxin-1 Proteins 0.000 abstract 2
- 101150035467 BDNF gene Proteins 0.000 abstract 2
- 102100029707 DnaJ homolog subfamily B member 4 Human genes 0.000 abstract 2
- 102100037334 E3 ubiquitin-protein ligase CHIP Human genes 0.000 abstract 2
- 102100040015 Eukaryotic translation initiation factor 2 subunit 3 Human genes 0.000 abstract 2
- -1 GCA Proteins 0.000 abstract 2
- 102100040352 Heat shock 70 kDa protein 1A Human genes 0.000 abstract 2
- 101000866008 Homo sapiens DnaJ homolog subfamily B member 4 Proteins 0.000 abstract 2
- 101000879619 Homo sapiens E3 ubiquitin-protein ligase CHIP Proteins 0.000 abstract 2
- 101000959829 Homo sapiens Eukaryotic translation initiation factor 2 subunit 3 Proteins 0.000 abstract 2
- 101001037759 Homo sapiens Heat shock 70 kDa protein 1A Proteins 0.000 abstract 2
- 101000735893 Homo sapiens Proteasome subunit beta type-6 Proteins 0.000 abstract 2
- 101000616974 Homo sapiens Pumilio homolog 1 Proteins 0.000 abstract 2
- 101000779418 Homo sapiens RAC-alpha serine/threonine-protein kinase Proteins 0.000 abstract 2
- 101000588548 Homo sapiens Serine/threonine-protein kinase Nek8 Proteins 0.000 abstract 2
- 101000588553 Homo sapiens Serine/threonine-protein kinase Nek9 Proteins 0.000 abstract 2
- 101000864800 Homo sapiens Serine/threonine-protein kinase Sgk1 Proteins 0.000 abstract 2
- 108010025026 Ku Autoantigen Proteins 0.000 abstract 2
- 102100036128 Proteasome subunit beta type-6 Human genes 0.000 abstract 2
- 102100021672 Pumilio homolog 1 Human genes 0.000 abstract 2
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 abstract 2
- 102100031398 Serine/threonine-protein kinase Nek9 Human genes 0.000 abstract 2
- 102100030070 Serine/threonine-protein kinase Sgk1 Human genes 0.000 abstract 2
- 102100036976 X-ray repair cross-complementing protein 6 Human genes 0.000 abstract 2
- 210000004027 cell Anatomy 0.000 abstract 2
- 239000013604 expression vector Substances 0.000 abstract 2
- 102000004196 processed proteins & peptides Human genes 0.000 abstract 2
- 238000002560 therapeutic procedure Methods 0.000 abstract 2
- 102100038222 60 kDa heat shock protein, mitochondrial Human genes 0.000 abstract 1
- 102100029374 Adapter molecule crk Human genes 0.000 abstract 1
- 108010058432 Chaperonin 60 Proteins 0.000 abstract 1
- 101000919320 Homo sapiens Adapter molecule crk Proteins 0.000 abstract 1
- 241000713666 Lentivirus Species 0.000 abstract 1
- 208000012902 Nervous system disease Diseases 0.000 abstract 1
- 208000025966 Neurological disease Diseases 0.000 abstract 1
- 102000003890 RNA-binding protein FUS Human genes 0.000 abstract 1
- 108090000292 RNA-binding protein FUS Proteins 0.000 abstract 1
- 210000001185 bone marrow Anatomy 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 abstract 1
- 230000008878 coupling Effects 0.000 abstract 1
- 238000010168 coupling process Methods 0.000 abstract 1
- 238000005859 coupling reaction Methods 0.000 abstract 1
- 230000003013 cytotoxicity Effects 0.000 abstract 1
- 231100000135 cytotoxicity Toxicity 0.000 abstract 1
- 239000000412 dendrimer Substances 0.000 abstract 1
- 229920000736 dendritic polymer Polymers 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 230000014509 gene expression Effects 0.000 abstract 1
- 230000001404 mediated effect Effects 0.000 abstract 1
- 239000002105 nanoparticle Substances 0.000 abstract 1
- 230000032405 negative regulation of neuron apoptotic process Effects 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 230000001172 regenerating effect Effects 0.000 abstract 1
- 210000001519 tissue Anatomy 0.000 abstract 1
- 238000001890 transfection Methods 0.000 abstract 1
- 238000002054 transplantation Methods 0.000 abstract 1
- 230000006648 viral gene expression Effects 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/0005—Vertebrate antigens
- A61K39/0007—Nervous system antigens; Prions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/515—Animal cells
- A61K2039/5156—Animal cells expressing foreign proteins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/51—Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
- A61K2039/53—DNA (RNA) vaccination
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/60—Medicinal preparations containing antigens or antibodies characteristics by the carrier linked to the antigen
- A61K2039/6031—Proteins
- A61K2039/6043—Heat shock proteins
Abstract
The present invention comprises methods for preparing a hybrid vaccine, which consists of an autologous solution of genetically modified mesenchymatic germ cells with human neuroprotective genes (siRNA) and transplantation thereof in the brain for the therapy of polyglutamine diseases for the treatment of the Huntingtons disease, and Spinocerebellar ataxia type 1 and Spinocerebellar ataxia type 3 by transfection of germ cells with gene expression vectors or lentiviruses containing viral gene expression vectors for the human neuroprotective genes. The neuroprotective genes are the (siRNA) CRK, DNAJB4, EIF2S3, GCA, NEK8, PSMB6, and PUM1, HTT, TBP, ATXN1, AR, Bdnf, AKT1, XRCC6, FUS, STUB1, HSPA1A, SGK1. The mesenchymatic cells constitute an interesting class of germ cells, since they can be easily isolated from bone marrow. These cells are very important in regenerative medicine, since they are pluripotent and can differentiate in various tissues. The genetically modified germ cells expressing neuroprotective proteins may aid in neuron survival, reducing the polyQ-mediated cytotoxicity and clearing the polyQ aggregates from the brain. These methods may be particularly useful for the treatment of polyglutamine diseases (Huntingtons disease, and Spinocerebellar ataxia type 1 and Spinocerebellar ataxia type 3). The present invention also comprises a method for transplanting genetically modified mesenchymatic germ cells in the brain for the prevention and/or treatment of neurological disorders associated with mutated proteins containing major polyglutamine extensions. The present invention describes the methods and the composition of a hybrid vaccine consisting of the product from the chemical reaction of a bipolar coupling of a polyQ peptide and the HSP60 peptide in molar ratio 1:1, which may elicit a strong immune response against the protein aggregates formed by mutated proteins with dominant extensions and polyglutamine inserts in the brain. The present hybrid vaccine may be proved particularly useful in the therapy of polyglutamine diseases for the treatment of Huntingtons disease, Spinocerebellar ataxia type 1 and Spinocerebellar ataxia type 3. The present invention also provides a hybrid vaccine composition containing an autologous solution of genetically modified mesenchymatic germ cells with the (siRNA) of consensus common coding sequences (CCCS) of the human neuroprotective genes (siRNA) CRK DNAJB4 EIF2S3 GCA NEK8 PSMB6 PUM1 and (siRNA) of consensus common coding sequences (CCCS) of genes HTT TBP ATXN1 AR Bdnf AKT1 XRCC6 FUS STUB1 HSPA1A SGK1 and a mixture of synthetic peptides comprising the PQ1 (SEQ ID.:1) and p458h (SEQ ID:2) peptides in a synthetic dendrimer nanoparticle composition carrier.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GR20110100262A GR20110100262A (en) | 2011-05-02 | 2011-05-02 | Hybrid gene peptidomimetic vaccine for immunological response of patients having polyq diseases. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GR20110100262A GR20110100262A (en) | 2011-05-02 | 2011-05-02 | Hybrid gene peptidomimetic vaccine for immunological response of patients having polyq diseases. |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GR20110100262A true GR20110100262A (en) | 2013-01-22 |
Family
ID=45491627
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GR20110100262A GR20110100262A (en) | 2011-05-02 | 2011-05-02 | Hybrid gene peptidomimetic vaccine for immunological response of patients having polyq diseases. |
Country Status (1)
| Country | Link |
|---|---|
| GR (1) | GR20110100262A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107406513A (en) * | 2014-07-25 | 2017-11-28 | 中央研究院 | Duplex molecule (BIPARTITE) and its purposes in treatment aberrant protein aggregations |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002016644A1 (en) * | 2000-08-18 | 2002-02-28 | Massachusetts Institute Of Technology | Inhibition of protein-protein interaction |
| WO2003045128A2 (en) * | 2001-11-21 | 2003-06-05 | New York University | SYNTHETIC IMMUNOGENIC BUT NON-DEPOSIT-FORMING POLYPEPTIDES AND PEPTIDES HOMOLOGOUS TO AMYLOID β, PRION PROTEIN, AMYLIN, α-SYNUCLEIN, OR POLYGLUTAMINE REPEATS FOR INDUCTION OF AN IMMUNE RESPONSE THERETO |
| WO2009090650A2 (en) * | 2008-01-16 | 2009-07-23 | Ben-Gurion University Of The Negev Research And Development Authority | Vaccine for alzheimer's disease |
| WO2011042872A1 (en) * | 2009-10-08 | 2011-04-14 | Universite Paris Diderot - Paris 7 | Use of a dna replication inhibitor for treating neurodegenerative diseases caused by polyglutamine expansion |
-
2011
- 2011-05-02 GR GR20110100262A patent/GR20110100262A/en not_active IP Right Cessation
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002016644A1 (en) * | 2000-08-18 | 2002-02-28 | Massachusetts Institute Of Technology | Inhibition of protein-protein interaction |
| WO2003045128A2 (en) * | 2001-11-21 | 2003-06-05 | New York University | SYNTHETIC IMMUNOGENIC BUT NON-DEPOSIT-FORMING POLYPEPTIDES AND PEPTIDES HOMOLOGOUS TO AMYLOID β, PRION PROTEIN, AMYLIN, α-SYNUCLEIN, OR POLYGLUTAMINE REPEATS FOR INDUCTION OF AN IMMUNE RESPONSE THERETO |
| WO2009090650A2 (en) * | 2008-01-16 | 2009-07-23 | Ben-Gurion University Of The Negev Research And Development Authority | Vaccine for alzheimer's disease |
| WO2011042872A1 (en) * | 2009-10-08 | 2011-04-14 | Universite Paris Diderot - Paris 7 | Use of a dna replication inhibitor for treating neurodegenerative diseases caused by polyglutamine expansion |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107406513A (en) * | 2014-07-25 | 2017-11-28 | 中央研究院 | Duplex molecule (BIPARTITE) and its purposes in treatment aberrant protein aggregations |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| ML | Lapse due to non-payment of fees |
Effective date: 20141203 |