EP0525091A1 - Test de diagnostic pour la sclerose en plaques - Google Patents

Test de diagnostic pour la sclerose en plaques

Info

Publication number
EP0525091A1
EP0525091A1 EP91908712A EP91908712A EP0525091A1 EP 0525091 A1 EP0525091 A1 EP 0525091A1 EP 91908712 A EP91908712 A EP 91908712A EP 91908712 A EP91908712 A EP 91908712A EP 0525091 A1 EP0525091 A1 EP 0525091A1
Authority
EP
European Patent Office
Prior art keywords
patient
plasma
protein
multiple sclerosis
blood
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Withdrawn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
EP91908712A
Other languages
German (de)
English (en)
Other versions
EP0525091A4 (fr
Inventor
Roy L. Swank
Roy A. Garvin
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.)
Individual
Original Assignee
Individual
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 Individual filed Critical Individual
Publication of EP0525091A1 publication Critical patent/EP0525091A1/fr
Publication of EP0525091A4 publication Critical patent/EP0525091A4/en
Withdrawn legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • G01N33/6896—Neurological disorders, e.g. Alzheimer's disease
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/28—Neurological disorders
    • G01N2800/285—Demyelinating diseases; Multipel sclerosis

Definitions

  • the present invention relates to a test and treatment for multiple sclerosis.
  • the present invention recognizes a distinct and reproducible difference between the plasma of MS patients and controls, consisting of the detectable presence in fasting MS patients of a protein not found in fasting control subjects.
  • the protein has an apparent molecular weight of around 67,000 Daltons, and has been tentatively identified as a plasma-derived transfer protein.
  • MS can be diagnosed by testing for the presence of such a protein in the blood plasma of fasting subjects.
  • the protein thus associated with MS exhibits many of the characteristics of the previously isolated phospholipid transfer protein (LTP II) , [ref: Albers, et al. Isolation and characterization of a phospholipid transfer protein (LTP II) from human plasma, J. of Lipid Research, Vol 29, 1988, pp 1593-1602], although it has not been positively identified as such.
  • MS patients could be treated by introducing a purified form of this or a related protein obtained from normal plasma into patients with MS. This treatment has not yet been clinically tested and proven, but appears promising as a result of the changes seen in blood samples obtained from MS patients after such laboratory treatment.
  • This protein is the only abnormality yet discovered in the plasma of MS patients, and it is thought that it may in fact be the factor which is altered to achieve the improvement seen to result from clinical infusion of normal plasma into MS patients.
  • FIG. 1 is a view of a densitometer readout of a polyacrylamide gel of albumin deficient plasma from an MS patient.
  • FIG. 2 is a representation of a polyacrylamide gel of albumin, albumin-deficient plasma samples from MS patients and controls, and molecular weight markers.
  • multiple sclerosis can be diagnosed definitely and at an earlier stage than has previously been possible, by detecting the presence of a protein which is not present in detectable quantities in fasting persons without MS.
  • the validity of this diagnosis was studied using blood from 63 subjects.
  • the samples used in this study were matched for sex, age and diet for a total of 31 controls and 32 MS patients ranging in age from 23-63 years. Thirty percent in both groups were female and 80% were on a low fat diet.
  • the MS patient diet consisted of 20 grams of saturated fat per day or less; the controls consumed up to 40 grams of saturated fat per day.
  • SDS-PAGE Sodium Dodecyl Sulfate Polyacrylamide Gel Electrophoresis
  • Readouts from the scanning densitometer showed three differences between plasma from controls and that from the MS patients. These differences were observed in the portions of the plasma whose molecular weights were in the range of 20,000-35,000 Daltons, and at approxi ⁇ mately 67,000 and 100,000 Daltons. In the 20,000-35,000 Dalton range the difference consisted mainly of slight differences in the peaks of low molecular-weight proteins in MS samples. However, they did not follow any set pattern, and their significance is therefore doubtful.
  • peak 10 represents residual albumin in a plasma sample from a fasting MS patient
  • peak 12 represents the protein observed in fasting MS patients but not in fasting subjects without MS.
  • FIG. 2 a representation of a polyacrylamide gel, shows a band 14 of an increased protein mass in albumin-deficient MS plasma samples A, B, C, D when compared to control samples E, F, G.
  • the protein present in samples A, B, C , D appears to have a molecular weight around 67,000 Daltons.
  • the plasma of MS patients responds to food intake by exhibiting increasing amounts of this protein. This protein was tentatively identified as a plasma derived lipid transfer protein.
  • a definite and reliable assay can be employed for the clinical diagnosis of MS, to detect the disease during or perhaps before the onset of symptoms.
  • the easiest and most reliable form of this assay would be one of several well known antibody detection procedures.
  • the assay could take several forms, such as an Enzyme Linked Immunoabsorbance Assay (ELISA) , immunodiffusion, i munoelectrophoresis or other protein detection systems.
  • ELISA Enzyme Linked Immunoabsorbance Assay
  • EXAMPLE Albumin was removed from the blood of a fasting (greater than eight hours) subject with an Affi-Gel Blue column from Pharmacia Biochemicals, Uppsala, Sweden, (1.5 x 10 cm) according to the manufacturers directions.
  • the plasma proteins were then separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) , with a 7.5% separating gel.
  • Molecular weight markers used during electrophoresis were prestained SDS-7B obtained through Sigma Chemical Company.
  • the resultant gels were stained with coammassie blue, and destained in 10% acetic acid and 15% methanol overnight. After destaining, the gels were preserved by air drying between sheets of biomembrane obtained from Biodesign of New York in accordance with their protocol. This procedure was performed with no heat added, in order to minimize distortion of the gels.
  • MS-associated protein indicates an abnormality in the plasma. Because the protein found in elevated quantities is metabolically related, presence of the protein in MS patients in a fasting state would indicate an abnormality in the metabolism of MS patients, and could be indicative of an abnormality in the protein. This is believed to be true because it has been shown that patients on a low fat diet have fewer and less severe exacerbations. Therefore infusion of a complementary metabolic protein from normal plasma could stabilize the patient's metabolism.

Landscapes

  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Hematology (AREA)
  • Chemical & Material Sciences (AREA)
  • Urology & Nephrology (AREA)
  • Molecular Biology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Medicinal Chemistry (AREA)
  • Microbiology (AREA)
  • Biotechnology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Food Science & Technology (AREA)
  • Cell Biology (AREA)
  • Physics & Mathematics (AREA)
  • Analytical Chemistry (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
  • Other Investigation Or Analysis Of Materials By Electrical Means (AREA)

Abstract

Il s'agit d'un test permettant de diagnostiquer la sclérose en plaques, lequel sert à identifier un taux anormalement élevé d'une protéine métabolique ayant une masse molaire égale à environ 67 000 Daltons dans le plasma sanguin. Un procédé de traitement comprend l'introduction, chez le patient, d'une certaine quantité de protéine similaire ou apparentée provenant du plasma correspondant.
EP91908712A 1990-03-30 1991-04-01 Test de diagnostic pour la sclerose en plaques Withdrawn EP0525091A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US50225890A 1990-03-30 1990-03-30
US502258 1990-03-30

Publications (2)

Publication Number Publication Date
EP0525091A1 true EP0525091A1 (fr) 1993-02-03
EP0525091A4 EP0525091A4 (fr) 1994-03-23

Family

ID=23997019

Family Applications (1)

Application Number Title Priority Date Filing Date
EP91908712A Withdrawn EP0525091A1 (fr) 1990-03-30 1991-04-01 Test de diagnostic pour la sclerose en plaques

Country Status (3)

Country Link
EP (1) EP0525091A1 (fr)
CA (1) CA2083583A1 (fr)
WO (1) WO1991015765A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4810657A (en) * 1987-10-19 1989-03-07 Swank Roy L Method of diagnosing multiple sclerosis and other diseases by measurement of blood plasma protein streaming potential

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL8501682A (nl) * 1985-06-11 1987-01-02 Tno Nieuw, uit bloed geisoleerd eiwit, werkwijze ter bereiding van dit eiwit, antilichamen tegen het nieuwe eiwit en farmaceutische preparaten, die het eiwit of de antilichamen bevatten.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4810657A (en) * 1987-10-19 1989-03-07 Swank Roy L Method of diagnosing multiple sclerosis and other diseases by measurement of blood plasma protein streaming potential

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
CLINICAL RESEARCH vol. 28, no. 2 , 1980 , WASHINGTON DC USA page 255A J. ALLEN ET AL. 'Plasma peptide concentrations in patients with multiple sclerosis (MS).' *
See also references of WO9115765A1 *

Also Published As

Publication number Publication date
CA2083583A1 (fr) 1991-10-01
EP0525091A4 (fr) 1994-03-23
WO1991015765A1 (fr) 1991-10-17

Similar Documents

Publication Publication Date Title
JP5264026B2 (ja) 心疾患の早期発見のための方法
KR100528664B1 (ko) 당뇨망막증 진단용 조성물 및 당뇨망막증 진단용 키트
Leonardi et al. Cerebrospinal fluid (CSF) findings in amyotrophic lateral sclerosis
US8846413B2 (en) Method for determining the concentration of the adipocytic form of the fatty acid binding protein (A-FABP, FABP4, P2)
KR20150052311A (ko) Ｆｔ-ｉｃｒ-ｍｓ/ｍｓ를 이용한 치은염 및 치주염의 바이오마커에 대한 타액 프로테옴의 분석
EP2657706A1 (fr) Biomarqueur pour des maladies de dysfonctionnement cognitif, et procédé de détection de maladies de dysfonctionnement cognitif à l'aide du biomarqueur
KR100689995B1 (ko) 알돌라제를 포함하는 망막혈관 질환 진단용 조성물 및 그진단방법
US20050124011A1 (en) Diagnosis of disease using tears
Rudman et al. Novel proteins and peptides in the urine of patients with advanced neoplastic disease
WO2010004962A1 (fr) Méthode de détection de la fibromyalgie
Saito et al. Marked increases in concentrations of apolipoprotein in the cerebrospinal fluid of poliovirus-infected macaques: relations between apolipoprotein concentrations and severity of brain injury
Campbell et al. The negative acute phase response of serum transthyretin following Streptococcus suis infection in the pig
Gelman et al. Cerebrospinal fluid and plasma apolipoproteins in patients with multiple sclerosis
Ohta et al. Carbonic anhydrase III in serum in muscular dystrophy and other neurological disorders: relationship with creatine kinase
Rozek et al. Sera proteomic biomarker profiling in HIV‐1 infected subjects with cognitive impairment
EP0525091A1 (fr) Test de diagnostic pour la sclerose en plaques
Weaver et al. Aged amylase: a valuable test for detecting and tracking pancreatic pseudocysts
JPH1090263A (ja) アルツハイマー病の診断のためのｅｒｋ−１およびｅｒｋ−２の利用
AU2003266881A1 (en) Process for differential diagnosis of alzheimer's dementia in patients exhibiting mild cognitive impairment
KR100817543B1 (ko) 당뇨망막증 진단용 단백질
US7070760B1 (en) Skin test for schizophrenia
Grataroli et al. Detection of the cystic fibrosis protein by isoelectric focusing of serum and plasma
SU1644038A1 (ru) Способ вы влени лиц с повышенным риском развити коагулопатии потреблени при гипертермических процедурах
US20060269963A1 (en) Composition for the diagnosis of retinal vascular disease comprising aldolase and method for diagnosis using it
SU1066551A1 (ru) Способ диагностики активности туберкулеза легких

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 19921124

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU NL SE

A4 Supplementary search report drawn up and despatched

Effective date: 19940202

AK Designated contracting states

Kind code of ref document: A4

Designated state(s): AT BE CH DE DK ES FR GB GR IT LI LU NL SE

17Q First examination report despatched

Effective date: 19940818

GRAG Despatch of communication of intention to grant

Free format text: ORIGINAL CODE: EPIDOS AGRA

GRAG Despatch of communication of intention to grant

Free format text: ORIGINAL CODE: EPIDOS AGRA

GRAG Despatch of communication of intention to grant

Free format text: ORIGINAL CODE: EPIDOS AGRA

GRAH Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOS IGRA

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN

18D Application deemed to be withdrawn

Effective date: 19970909