EP0917573A2 - 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

Info

Publication number
EP0917573A2
EP0917573A2 EP97935447A EP97935447A EP0917573A2 EP 0917573 A2 EP0917573 A2 EP 0917573A2 EP 97935447 A EP97935447 A EP 97935447A EP 97935447 A EP97935447 A EP 97935447A EP 0917573 A2 EP0917573 A2 EP 0917573A2
Authority
EP
European Patent Office
Prior art keywords
cell
nervous system
peripheral nervous
protein
autoimmune diseases
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.)
Withdrawn
Application number
EP97935447A
Other languages
German (de)
English (en)
Inventor
Ralf Gold
Andreas Weishaupt
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
GOLD, RALF
Weishaupt Andreas
Original Assignee
Weishaupt Andreas
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 Weishaupt Andreas filed Critical Weishaupt Andreas
Publication of EP0917573A2 publication Critical patent/EP0917573A2/fr
Withdrawn legal-status Critical Current

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.
EP97935447A 1996-07-18 1997-07-18 Proteine de myeline recombinee pour traiter des affections auto-immunes induites par cellules t Withdrawn EP0917573A2 (fr)

Applications Claiming Priority (3)

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 1996-07-18
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

Publications (1)

Publication Number Publication Date
EP0917573A2 true EP0917573A2 (fr) 1999-05-26

Family

ID=7800236

Family Applications (1)

Application Number Title Priority Date Filing Date
EP97935447A Withdrawn EP0917573A2 (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)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0329760A4 (en) * 1987-08-11 1990-12-27 Univ South Carolina Suppressive t lymphocyte cell lines and supernatant derivative thereof
EP0725277A3 (fr) * 1990-05-01 1996-12-04 Univ Leland Stanford Junior Transcrits variables de récepteurs de lymphocytes T utilisés comme marqueurs relatifs à des maladies
WO1995007096A1 (fr) * 1993-09-06 1995-03-16 La Trobe University Traitement de maladies auto-immunes

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9803647A3 *

Also Published As

Publication number Publication date
WO1998003647A3 (fr) 1998-04-09
AU3846297A (en) 1998-02-10
DE19629095A1 (de) 1998-02-12
WO1998003647A2 (fr) 1998-01-29

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