WO1998003647A2 - Proteine de myeline recombinee pour traiter des affections auto-immunes induites par cellules t - Google Patents

Proteine de myeline recombinee pour traiter des affections auto-immunes induites par cellules t Download PDF

Info

Publication number
WO1998003647A2
WO1998003647A2 PCT/DE1997/001535 DE9701535W WO9803647A2 WO 1998003647 A2 WO1998003647 A2 WO 1998003647A2 DE 9701535 W DE9701535 W DE 9701535W WO 9803647 A2 WO9803647 A2 WO 9803647A2
Authority
WO
WIPO (PCT)
Prior art keywords
cell
nervous system
peripheral nervous
protein
autoimmune diseases
Prior art date
Application number
PCT/DE1997/001535
Other languages
German (de)
English (en)
Other versions
WO1998003647A3 (fr
Inventor
Ralf Gold
Andreas Weishaupt
Original Assignee
Ralf Gold
Andreas Weishaupt
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Ralf Gold, Andreas Weishaupt filed Critical Ralf Gold
Priority to EP97935447A priority Critical patent/EP0917573A2/fr
Priority to AU38462/97A priority patent/AU3846297A/en
Priority to US09/214,943 priority patent/US6319892B1/en
Publication of WO1998003647A2 publication Critical patent/WO1998003647A2/fr
Publication of WO1998003647A3 publication Critical patent/WO1998003647A3/fr

Links

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
    • A61K38/1703—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

Definitions

  • the invention relates to the use of recombinant myelin protein for the treatment of T cell-mediated autoimmune diseases of the peripheral nervous system.
  • autoimmune genetics have been treated by immunosuppressive or immunomodulating therapy.
  • common treatment methods are the administration of steroids (e.g. cortisone), immunoglobulins and long-term immunosuppressive drugs (e.g. azathiopm) or the implementation of plasmaphoresis.
  • steroids e.g. cortisone
  • immunoglobulins e.g. azathiopm
  • long-term immunosuppressive drugs e.g. azathiopm
  • the object of the present invention is therefore to provide a possibility with which T-cell-mediated autoimmune diseases of the peripheral nervous system can be treated successfully and gently.
  • autoimmune B-cell and T-cell responses directed against pe ⁇ phere myelin components play an important role in the pathogenesis of inflammatory demyelinating diseases of the nervous system.
  • diseases are known as immune neuropathies of the peripheral nervous system, e.g. chronic inflammatory polyneuropathy,
  • T-lymphocytes are generated, which are specific for structural proteins of the myelin of the peripheral nervous system and lead to demyelination and inflammation in the peripheral nervous system.
  • This model disease is representative of the aforementioned autoimmune diseases of the peripheral nervous system, in which an increased number of T cells, demyelination and nerve inflammation also occur.
  • T cell mediated autoimmune disorders of the peripheral nervous system by administration of high doses of the autoantigen, i.e. can be reversed or at least improved by high-dose administration of myelin protein.
  • This therapy is called high-dose antigen therapy and leads to a gentle death of the T cells (T cell apoptosis), which is ultimately responsible for the triggering and the course of the
  • Intravenous injection is particularly preferred.
  • myelin proteins such as PO, peripheral myelin glycolipids (eg GM 1), MBP, PLP, MOG, MAG, S-100 protein and in particular P2 are suitable as the autoantigen to be administered.
  • myelin protein should be understood to include mixtures of different proteins, protein fragments and mixtures of protein fragments. It should be emphasized that these proteins should have been produced recombinantly, since it is very expensive and time-consuming to purify the proteins in sufficient quantities from natural myelin . In addition, when using purified protein from bovine nerve myelin, BSE can easily be transmitted.
  • Fig. 1 A + B Treatment of EAN with different doses of rhP2
  • Fig. 2 Suppression of a rat T cell line by administration of antigen in high doses
  • Fig. 3 A Immunocytochemical analysis of T cell infiltration in rhP2-treated rats and rhPO control animals in the presence of EAN. The values are given as the mean density of T cells / mm 2 ⁇ standard deviation of 3 animals / group.
  • Fig. 3 B T cell apoptosis in treated animals compared to spontaneous T cell apoptosis in control animals.
  • the values are given as the mean density of apoptotic cells / mm 2 ⁇ standard deviation of 3 animals / group.
  • Fig. 4 Nucleotide sequence and corresponding amino acid sequence of the human recombinant (complete sequence) and bovine P2 proteins (only the amino acid exchanges are given). Introduced restriction enzyme sites and histidine tail sequences are underlined.
  • mice Female Lewis rats (age: 6-8 weeks; weight: 1 25-1 60 g) were used.
  • Neuritogenic P2-specific T cell lines G5 and G7 were produced as described in "Linington et al., J. Immunol. 1 33, 1 946- 1 950 (1 984)".
  • the rats which had been injected with 8 ⁇ 10 6 P2-specific T cells, were divided into different groups 3 days after the T cell injection:
  • Group 1 received 500 ⁇ g rhP2 twice a day
  • Group 2 received 100 ⁇ g rhPO twice daily
  • group 3 received 100 ⁇ g rhP2 twice daily
  • group 4 received 500 ⁇ g ovalbumin twice daily.
  • T cells were incubated with increasing doses of rhP2 or the neuritogenic P2 peptide (amino acids 53-78).
  • rhP2 or the neuritogenic P2 peptide amino acids 53-78.
  • 1.5 x 10 4 responder G5 or G7 T cells, 7.5 x 10 5 irradiated (3000 rad) thymocytes and various concentrations of rhP2 or the neuritogenic P2 peptide in a total volume of 100 ⁇ l per well were mixed into one 96-well microtiter plate filled. After 48 hours, the cells were labeled with 0.2 ⁇ Ci / well 3 H-dT for 16 hours and harvested at the indicated time. The cells were collected on a glass fiber filter paper and the radioactivity distribution was evaluated.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Marine Sciences & Fisheries (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Zoology (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)

Abstract

L'invention concerne l'utilisation de protéine de myéline recombinée pour traiter des affections auto-immunes du système nerveux périphérique induites par cellules T.
PCT/DE1997/001535 1996-07-18 1997-07-18 Proteine de myeline recombinee pour traiter des affections auto-immunes induites par cellules t WO1998003647A2 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
EP97935447A EP0917573A2 (fr) 1996-07-18 1997-07-18 Proteine de myeline recombinee pour traiter des affections auto-immunes induites par cellules t
AU38462/97A AU3846297A (en) 1996-07-18 1997-07-18 Use of recombinant myelin protein for treating t-cell-mediated autoimmune diseases of the peripheral nervous system
US09/214,943 US6319892B1 (en) 1997-07-18 1997-07-18 Use of recombinant myelin protein for treating T-cell-mediated autoimmune diseases of the peripheral nervous system

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE1996129095 DE19629095A1 (de) 1996-07-18 1996-07-18 Verwendung von rekombinantem Myelinprotein zur Behandlung von T-Zell vermittelten Autoimmunerkrankungen des peripheren Nervensystems
DE19629095.3 1996-07-18

Publications (2)

Publication Number Publication Date
WO1998003647A2 true WO1998003647A2 (fr) 1998-01-29
WO1998003647A3 WO1998003647A3 (fr) 1998-04-09

Family

ID=7800236

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DE1997/001535 WO1998003647A2 (fr) 1996-07-18 1997-07-18 Proteine de myeline recombinee pour traiter des affections auto-immunes induites par cellules t

Country Status (4)

Country Link
EP (1) EP0917573A2 (fr)
AU (1) AU3846297A (fr)
DE (1) DE19629095A1 (fr)
WO (1) WO1998003647A2 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991017268A1 (fr) * 1990-05-01 1991-11-14 The Board Of Trustees Of The Leland Stanford Junior University Transcrits variables de recepteurs de lymphocytes t utilises comme marqueurs relatifs a des maladies
WO1995007096A1 (fr) * 1993-09-06 1995-03-16 La Trobe University Traitement de maladies auto-immunes

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1989001511A1 (fr) * 1987-08-11 1989-02-23 Medical University Of South Carolina Lignees cellulaires de lymphocytes t suppresseurs et leurs derives surnageants

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1991017268A1 (fr) * 1990-05-01 1991-11-14 The Board Of Trustees Of The Leland Stanford Junior University Transcrits variables de recepteurs de lymphocytes t utilises comme marqueurs relatifs a des maladies
WO1995007096A1 (fr) * 1993-09-06 1995-03-16 La Trobe University Traitement de maladies auto-immunes

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
A. KHALILI-SHIRAZI ET AL.: "T CELL RESPONSES TO MYELIN PROTEINS IN GUILLIN-BARRÉ SYNDROME." JOURNAL OF NEUROLOGICAL SCIENCES, Bd. 111, Nr. 2, September 1992, AMSTERDAM, NL, Seiten 200-203, XP002052788 *
A. WEISHAUPT ET AL.: "ANTIGEN THERAPY ELIMINATES T CELL INFLAMMATION BY APOPTOSIS: EFFECTIVE TREATMENT OF EXPERIMENTAL AUTOIMMUNE NEURITIS WITH RECOMBINANT MAELIN PROTEIN P2." PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF USA, Bd. 94, Februar 1997, WASHINGTON US, Seiten 1338-1343, XP002052789 *
A. WEISHAUPT ET AL.: "T CELL ANTIGENIC AND NEURITOGENIC ACTIVITY OF RECOMBINANT HUMAN PERIPHERAL MYELIN P2 PROTEIN." JOURNAL OF NEUROIMMUNOLOGY, Bd. 63, Nr. 2, 31.Dezember 1995, AMSTERDAM, NL, Seiten 149-156, XP002052786 in der Anmeldung erw{hnt *
J.M. CRITCHFIELD ET AL.: "T CELL DELETION IN HIGH ANTIGEN DOSE THERAPY OF AUTOIMMUNE ENCEPHALOMYELITIS." SCIENCE, Bd. 263, 25.Februar 1994, LANCASTER, PA US, Seiten 1139-1143, XP002052787 *

Also Published As

Publication number Publication date
EP0917573A2 (fr) 1999-05-26
DE19629095A1 (de) 1998-02-12
AU3846297A (en) 1998-02-10
WO1998003647A3 (fr) 1998-04-09

Similar Documents

Publication Publication Date Title
DE69831971T2 (de) Unterdrückung von veränderungen in zusammenhang mit beta-amyloid bei alzheimer
DE69532996T2 (de) Peptidanaloge des menschlichen basischen myelinproteins
DE69127470T2 (de) Verstärkung der unterdrückungsregulation von autoimmunkrankheiten durch orale oder enterale verabreichung von autoantigenen
DE69233643T2 (de) Verwendung von Antizytokin-enthaltenden pharmazeutischen Zusammensetzungen zur Therapie von multipler Sklerose
Sato et al. Antiepileptic effects of thyrotropin‐releasing hormone and its new derivative, DN‐1417, examined in feline amygdaloid kindling preparation
EP0346501B1 (fr) Preparation pharmaceutique pour traiter des etats immunodeficitaires
DE69632967T2 (de) Verfahren zur Verhinderung der Transplantabstoßung bei einer Transplantation und zur Herstellung einer universalen Gentherapie-Wirtszelle unter Anwendung von Lymphocyten-Aktivierungsgen (LAG-3)
EP2085094A2 (fr) Utilisation d'inhibiteurs des alanyl-aminopeptidases et préparations pharmaceutiques en étant pourvues
Cain et al. Effects of protein synthesis inhibition on kindling in the mouse
US5200396A (en) Method of treating neurodegenerative disorders using epidermal growth factor
EP1171587A1 (fr) Peptide derive de l'antigene muc-1 destine a declencher une reaction immunitaire contre des cellules tumorales
FORTIER et al. A comparative study of some of the chemical and morphological changes elicited in the adrenals by stress and purified ACTH
EP0756605B1 (fr) Peptides utilise comme agents therapeutiques dans le traitement de maladies auto-immunes
Sato et al. An analysis of anticonvulsant actions of GABA agonists (progabide and baclofen) in the kindling model of epilepsy
DE60103685T2 (de) Behandlung von Poriomania
MX2007000144A (es) Medicamento.
EP2572724A1 (fr) Traitement de fibroses et de maladies du foie
Wada et al. Anticonvulsant effects of zonisamide and phenytoin on seizure activity of the feline visual cortex
EP1363658B1 (fr) Therapie genique utilisant beta-endorphin / crf pour combattre la douleur localement
WO1998003647A2 (fr) Proteine de myeline recombinee pour traiter des affections auto-immunes induites par cellules t
DE69626050T2 (de) Pharmazeutische zusammensetzung enthaltend interferon-gamma stimulatoren
US5830857A (en) Method of treating epilepsy
US6319892B1 (en) Use of recombinant myelin protein for treating T-cell-mediated autoimmune diseases of the peripheral nervous system
DE69532557T2 (de) Zubereitung enthaltend Glykane übereinstimmend mit Transferrin Glykaner als aktives Prinzip für die Induktion der Immuntoleranz gegen Antigene
WO2006114322A1 (fr) Utilisation de ligands de tlr et/ou de nod2 dans la fabrication d'un medicament destine au traitement d'une maladie du systeme nerveux central

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A2

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW AM AZ BY KG KZ MD RU TJ TM

AL Designated countries for regional patents

Kind code of ref document: A2

Designated state(s): GH KE LS MW SD SZ UG ZW AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
AK Designated states

Kind code of ref document: A3

Designated state(s): AL AM AT AU AZ BA BB BG BR BY CA CH CN CU CZ DE DK EE ES FI GB GE GH HU IL IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MD MG MK MN MW MX NO NZ PL PT RO RU SD SE SG SI SK SL TJ TM TR TT UA UG US UZ VN YU ZW AM AZ BY KG KZ MD RU TJ TM

AL Designated countries for regional patents

Kind code of ref document: A3

Designated state(s): GH KE LS MW SD SZ UG ZW AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
WD Withdrawal of designations after international publication

Free format text: DE

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 1997935447

Country of ref document: EP

WWE Wipo information: entry into national phase

Ref document number: 09214943

Country of ref document: US

NENP Non-entry into the national phase in:

Ref country code: CA

WWP Wipo information: published in national office

Ref document number: 1997935447

Country of ref document: EP

NENP Non-entry into the national phase in:

Ref country code: JP

Ref document number: 1998506457

Format of ref document f/p: F

REG Reference to national code

Ref country code: DE

Ref legal event code: 8642

WWW Wipo information: withdrawn in national office

Ref document number: 1997935447

Country of ref document: EP