BIOCHEMICAL STUDIES OF MYELINATION AND DEMYELINATION

Project: Research project

Description

We propose to study three major areas of closely related research
concerning the chemical pathology and the immunologic basis of
demyelination in multiple sclerosis and the biochemical and genetic basis
of myelinogenesis in a unique murine hypermyelination model. (1) A major
goal of the first area is to furnish reliable data on the chemical
composition of MS CNS tissues, especially that of spinal cord, cord myelin,
and the plaques, and to define the biochemical basis of myeline breakdown
and repair. There has not been any reliable diagnostic procedure for MS.
We have developed several novel and highly sensitive procedures for
analyzing a number of myelin-associated components. These procedures are
designed for the small amounts of CSF available from individual patients
and should be useful in providing objective and reliable indices for active
demyelination in MS patients. (2) Immunological research in MS has been
extensive but has not yet answered important questions regarding etiology,
diagnosis and treatment. However, there is strong evidence that an
autoimmune mechanism may play an important role in the pathogenesis of this
disease. The autoantigen(s) that are involved in myelin and
oligodendroglial degeneration in MS have not been clearly defined. We can
gain a better understanding of the nature of the specific antigens by
producing experimental disease in animals with various compounds,
particularly the compounds that are specifically localized in CNS myelin
and oligodendroglia. Additionally, the use of sensitive solid-phase
radioimmunoassay procedures for the detection of circulating antibodies in
MS should help answer the crucial question regarding the nature of the
autoantigen. (3) Finally, our plan to study myelinogenesis in a unique
hypermyelination model should provide us with a better understanding of the
effect of thyroid hormone on myelinogenesis, the regulation of myelin
synthesis, and the genetic factors governing myelination. An application
of this study is, of course, to consider the possibility of applying
hormonal therapy to enhance the remyelination process in MS patients. The
knowledge obtained from the entire project should be essential in improving
our diagnostic capability, in devising rational and effective therapies for
MS, as well as in providing vital information on myelinogenesis and its
normal function.
StatusFinished
Effective start/end date7/1/863/31/95

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Demyelinating Diseases
Myelin Sheath
Glycosphingolipids
Multiple Sclerosis
Galactosylceramides
Autoantigens
Endothelial Cells
Galactosyltransferases
Myelin Proteins
Encephalomyelitis
Antigens
Animal Diseases
Autoimmune Experimental Encephalomyelitis
Glycolipids
Oligodendroglia
Enzymes
Thyroid Hormones
Research
Endothelium
Blood Vessels

ASJC

  • Medicine(all)
  • Neuroscience(all)