Monoclonal remyelination-promoting natural autoantibody SCH 94.03: Pharmacokinetics and in vivo targets within demyelinated spinal cord in a mouse model of multiple sclerosis

Samuel F. Hunter, David J. Miller, Moses Rodriguez

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Chronic inflammatory demyelination of the central nervous system is usually incompletely repaired. However, we previously reported that in vivo treatment with monoclonal antibody SCH 94.03 (produced using spinal cord homogenate as an immunogen) increased myelin repair 4-fold in the Theiler's virus mouse model of chronic progressive multiple sclerosis (Miller et al., 1994; J. Neurosci. 14: 6230-6238). A major issue regarding site and mechanism of action of this antibody is whether SCH 94.03 enters demyelinated CNS lesions and reacts With oligodendrocytes and myelin. To address this question, we radiolabeled SCH 94.03 and studied its distribution into tissues, pharmacokinetics, and binding to cells within demyelinating spinal cord lesions in vivo. SCH 94.03 distributed widely into extracellular water following intraperitoneal injection and was eliminated with a terminal half-life of 3-4.5 days. Only a portion of the total dose (0.4%) entered brain and spinal cord. SCH 94.03 accumulated 1.5-2.0-fold in brain between 1 and 7 days after injection, but its pharmacokinetics were otherwise similar to those of an isotype control IgMκ antibody. Oligodendrocytes, myelin sheaths and, less frequently, axons were labeled within demyelinating lesions as detected by light and electron microscopic autoradiography. These findings suggest that remyelination-promoting autoantibodies could act within the demyelinating lesion of the central nervous system by binding to the oligodendrocyte, myelin, or axon.

Original languageEnglish (US)
Pages (from-to)103-113
Number of pages11
JournalJournal of the Neurological Sciences
Volume150
Issue number2
DOIs
StatePublished - Sep 10 1997

Fingerprint

Myelin Sheath
Autoantibodies
Multiple Sclerosis
Spinal Cord
Oligodendroglia
Pharmacokinetics
Axons
Central Nervous System
Theilovirus
Chronic Progressive Multiple Sclerosis
Antibodies
Brain
Demyelinating Diseases
Tissue Distribution
Intraperitoneal Injections
Autoradiography
Immunoglobulin M
Half-Life
Monoclonal Antibodies
Electrons

Keywords

  • Demyelination
  • Multiple sclerosis
  • Myelin
  • Natural autoantibody
  • Oligodendrocyte
  • Pharmacokinetics
  • Remyelination
  • Theiler's virus

ASJC Scopus subject areas

  • Aging
  • Clinical Neurology
  • Surgery
  • Developmental Neuroscience
  • Neurology
  • Neuroscience(all)

Cite this

Monoclonal remyelination-promoting natural autoantibody SCH 94.03 : Pharmacokinetics and in vivo targets within demyelinated spinal cord in a mouse model of multiple sclerosis. / Hunter, Samuel F.; Miller, David J.; Rodriguez, Moses.

In: Journal of the Neurological Sciences, Vol. 150, No. 2, 10.09.1997, p. 103-113.

Research output: Contribution to journalArticle

@article{c382070b3f754163ae8a210714611de0,
title = "Monoclonal remyelination-promoting natural autoantibody SCH 94.03: Pharmacokinetics and in vivo targets within demyelinated spinal cord in a mouse model of multiple sclerosis",
abstract = "Chronic inflammatory demyelination of the central nervous system is usually incompletely repaired. However, we previously reported that in vivo treatment with monoclonal antibody SCH 94.03 (produced using spinal cord homogenate as an immunogen) increased myelin repair 4-fold in the Theiler's virus mouse model of chronic progressive multiple sclerosis (Miller et al., 1994; J. Neurosci. 14: 6230-6238). A major issue regarding site and mechanism of action of this antibody is whether SCH 94.03 enters demyelinated CNS lesions and reacts With oligodendrocytes and myelin. To address this question, we radiolabeled SCH 94.03 and studied its distribution into tissues, pharmacokinetics, and binding to cells within demyelinating spinal cord lesions in vivo. SCH 94.03 distributed widely into extracellular water following intraperitoneal injection and was eliminated with a terminal half-life of 3-4.5 days. Only a portion of the total dose (0.4{\%}) entered brain and spinal cord. SCH 94.03 accumulated 1.5-2.0-fold in brain between 1 and 7 days after injection, but its pharmacokinetics were otherwise similar to those of an isotype control IgMκ antibody. Oligodendrocytes, myelin sheaths and, less frequently, axons were labeled within demyelinating lesions as detected by light and electron microscopic autoradiography. These findings suggest that remyelination-promoting autoantibodies could act within the demyelinating lesion of the central nervous system by binding to the oligodendrocyte, myelin, or axon.",
keywords = "Demyelination, Multiple sclerosis, Myelin, Natural autoantibody, Oligodendrocyte, Pharmacokinetics, Remyelination, Theiler's virus",
author = "Hunter, {Samuel F.} and Miller, {David J.} and Moses Rodriguez",
year = "1997",
month = "9",
day = "10",
doi = "10.1016/S0022-510X(97)00080-4",
language = "English (US)",
volume = "150",
pages = "103--113",
journal = "Journal of the Neurological Sciences",
issn = "0022-510X",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - Monoclonal remyelination-promoting natural autoantibody SCH 94.03

T2 - Pharmacokinetics and in vivo targets within demyelinated spinal cord in a mouse model of multiple sclerosis

AU - Hunter, Samuel F.

AU - Miller, David J.

AU - Rodriguez, Moses

PY - 1997/9/10

Y1 - 1997/9/10

N2 - Chronic inflammatory demyelination of the central nervous system is usually incompletely repaired. However, we previously reported that in vivo treatment with monoclonal antibody SCH 94.03 (produced using spinal cord homogenate as an immunogen) increased myelin repair 4-fold in the Theiler's virus mouse model of chronic progressive multiple sclerosis (Miller et al., 1994; J. Neurosci. 14: 6230-6238). A major issue regarding site and mechanism of action of this antibody is whether SCH 94.03 enters demyelinated CNS lesions and reacts With oligodendrocytes and myelin. To address this question, we radiolabeled SCH 94.03 and studied its distribution into tissues, pharmacokinetics, and binding to cells within demyelinating spinal cord lesions in vivo. SCH 94.03 distributed widely into extracellular water following intraperitoneal injection and was eliminated with a terminal half-life of 3-4.5 days. Only a portion of the total dose (0.4%) entered brain and spinal cord. SCH 94.03 accumulated 1.5-2.0-fold in brain between 1 and 7 days after injection, but its pharmacokinetics were otherwise similar to those of an isotype control IgMκ antibody. Oligodendrocytes, myelin sheaths and, less frequently, axons were labeled within demyelinating lesions as detected by light and electron microscopic autoradiography. These findings suggest that remyelination-promoting autoantibodies could act within the demyelinating lesion of the central nervous system by binding to the oligodendrocyte, myelin, or axon.

AB - Chronic inflammatory demyelination of the central nervous system is usually incompletely repaired. However, we previously reported that in vivo treatment with monoclonal antibody SCH 94.03 (produced using spinal cord homogenate as an immunogen) increased myelin repair 4-fold in the Theiler's virus mouse model of chronic progressive multiple sclerosis (Miller et al., 1994; J. Neurosci. 14: 6230-6238). A major issue regarding site and mechanism of action of this antibody is whether SCH 94.03 enters demyelinated CNS lesions and reacts With oligodendrocytes and myelin. To address this question, we radiolabeled SCH 94.03 and studied its distribution into tissues, pharmacokinetics, and binding to cells within demyelinating spinal cord lesions in vivo. SCH 94.03 distributed widely into extracellular water following intraperitoneal injection and was eliminated with a terminal half-life of 3-4.5 days. Only a portion of the total dose (0.4%) entered brain and spinal cord. SCH 94.03 accumulated 1.5-2.0-fold in brain between 1 and 7 days after injection, but its pharmacokinetics were otherwise similar to those of an isotype control IgMκ antibody. Oligodendrocytes, myelin sheaths and, less frequently, axons were labeled within demyelinating lesions as detected by light and electron microscopic autoradiography. These findings suggest that remyelination-promoting autoantibodies could act within the demyelinating lesion of the central nervous system by binding to the oligodendrocyte, myelin, or axon.

KW - Demyelination

KW - Multiple sclerosis

KW - Myelin

KW - Natural autoantibody

KW - Oligodendrocyte

KW - Pharmacokinetics

KW - Remyelination

KW - Theiler's virus

UR - http://www.scopus.com/inward/record.url?scp=0030752967&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030752967&partnerID=8YFLogxK

U2 - 10.1016/S0022-510X(97)00080-4

DO - 10.1016/S0022-510X(97)00080-4

M3 - Article

C2 - 9268236

AN - SCOPUS:0030752967

VL - 150

SP - 103

EP - 113

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

SN - 0022-510X

IS - 2

ER -