CFS, a combination of environment, genetics, immune system dysfunction
and possible viral involvement are suspected. Viral involvement in
many diseases is controversial not just in ME and CFS. Dr. Joseph
Brewer, an infectious disease specialist in Kansas City who sees many
ME and CFS patients, has theorized that MS and CFS are on a continuum
with CFS on the severe end of the continuum.
This particular study uses macaque monkeys whose bodies are more
similar to humans, however they are more expensive to use than mice.
An animal model is a living, non-human animal used during the research
and investigation of human disease, for the purpose of better
understanding the disease without the added risk of causing harm to an
actual human being during the process. The animal chosen will usually
meet a determined taxonomic equivalency to humans, so as to react to
disease or its treatment in a way that resembles human physiology as
needed.
MS-Like Disease Found in Monkeys
By John Gever, Senior Editor, MedPage Today
Published: July 01, 2011
Reviewed by Dori F. Zaleznik, MD; Associate Clinical Professor of
Medicine, Harvard Medical School, Boston.
Action Points
Explain that researchers studying a spontaneously arising
demyelinating disease in a research colony of Japanese macaque monkeys
have found that the disease closely resembles human multiple
sclerosis.
Note that a novel herpesvirus, most closely related to rhesus
rhadinovirus, was isolated from active white matter plaques in six
animals, but was not found in unaffected brain.
A potential new experimental model for multiple sclerosis, as well as
support for a viral origin of the disease, appears to have emerged
spontaneously among macaque monkeys in a research colony.
In the past 25 years, 56 Japanese macaques at the Oregon National
Primate Research Center in Beaverton, Ore., have developed a syndrome
marked by paresis of one or more limbs, ataxia, and/or ocular motor
paresis, according to the center's Scott W. Wong, PhD, and
colleagues...The latter finding is especially provocative because
herpes viruses, especially the Epstein-Barr virus, have long been
suspected as a possible etiologic agent or trigger for human MS.
A population-wide records study in Taiwan recently found thatshingles
attacks appeared to quadruple the risk of MS diagnosis within one
year. Shingles are caused by another herpes virus, the
varicella-zoster virus.
However, the so-called viral theory of MS has been controversial and
is certain to remain so in the wake of the new findings in macaques.
The discovery's most important short-term impact will likely be the
prospect of a new experimental model of the disease.
Currently, most animal studies are conducted in rodents with
experimental autoimmune encephalitis (EAE), which is induced by
injecting the animals with myelin proteins to provoke an immune attack
that cross-reacts with their own myelin-containing tissues.
It therefore is a good mimic of human MS, which is generally believed
to result from autoimmune attack on the myelin sheaths surrounding
nerve fibers in the peripheral and central nervous systems.
EAE can be induced in primates as well, but the main problem with it,
as an MS model, is that it does not arise spontaneously, whereas MS
does.
Thus, what appeared to be a serious problem at the Oregon center may
end up as serendipity.
Wong and colleagues explained that the outbred Japanese macaque colony
was founded in 1965 and no unusual neurologic diseases were seen until
1986, when the first case of unexplained paresis was spotted.
Eight more cases developed in 1987. Since then, from one to four
additional cases were seen in most years -- about 1% to 3% of animals
in the colony each year.
Most of the affected animals were euthanized quickly, a median of six
days after development of symptoms. However, three of the monkeys
appeared to recover, then developed recurrent symptoms up to eight
years later, prompting them to be euthanized.
In the eight animals having MRI scans, lesions were seen in all major
brain areas -- cerebrum, cerebellum, and brainstem -- and in the
cervical spinal cord.
Necropsies were performed in 54 of the animals, with no evidence of
disease outside the nervous system.
"In all cases, neuropathologic examination of the brain and cervical
spinal cord revealed a multifocal demyelinating encephalomyelitis,"
Wong and colleagues wrote....
The findings added up to clinical and pathological presentations
strongly resembling humans with MS, the researchers indicated.
Because viral infections have been conclusively linked to inflammatory
demyelination in mice, if not humans, Wong and colleagues also looked
for viruses in the macaques' acute lesions.
The search yielded "an infectious agent that was identified by
transmission electron micrography as a herpesvirus," they wrote. It
was then isolated and its genetic matter sequenced.
The sequence analysis indicated that the virus was previously unknown
to science, most closely resembling the rhesus macaque rhadinovirus
with 89.5% nucleotide homology.
It also shared about half of its sequence with the human Kaposi
sarcoma-associated herpesvirus.
Wong and colleagues reported that they were able to isolate the same
virus from active white-matter lesions in six animals. It appeared not
to be present in normal white matter from macaques with the MS-like
encephalitis or from healthy animals.
In addition to its spontaneous origin, the observation that only a few
animals in the colony developed the condition each year is another
point in its favor as a model for human MS, the researchers suggested.
It's an indication that "there may be a genetic susceptibility to the
disease, as there is in MS," they wrote.
"Interestingly, animals developing Japanese macaque encephalitis since
2000 come from distinct matrilines from the original troop, supporting
the idea that host genetic factors play a significant part in
susceptibility to disease," Wong and colleagues noted.
The researchers indicated that they were planning additional studies
of the immunology underlying the macaque disease, as well as the novel
herpesvirus's role.
The research was supported by the National Institutes of Health, the
Department of Veterans Affairs, and the U.S. Department of Defense.
One co-author reported research funding from Vertex Pharmaceuticals
and stock interest in DeltaPoint. Others declared they had no relevant
financial interests.
Primary source: Annals of Neurology
Source reference:
Axthelm M, et al "Japanese macaque encephalomyelitis: A spontaneous
multiple sclerosis -- like disease in a nonhuman primate" Ann Neurol
2011; DOI: 10.1002/ana.22449.
The full story can be read here:
http://www.medpagetoday.com/Neurology/MultipleSclerosis/27378?utm_content=&utm_medium=email&utm_campaign=DailyHeadlines&utm_source=WC&userid=267244
---------------------------------------------
Send posts to CO-CURE@listserv.nodak.edu
Unsubscribe at http://www.co-cure.org/unsub.htm
---------------------------------------------
Co-Cure's purpose is to provide information from across the spectrum of
opinion concerning medical, research and political aspects of ME/CFS and/or
FMS. We take no position on the validity of any specific scientific or
political opinion expressed in Co-Cure posts, and we urge readers to
research the various opinions available before assuming any one
interpretation is definitive. The Co-Cure website <www.co-cure.org> has a
link to our complete archive of posts as well as articles of central
importance to the issues of our community.
---------------------------------------------
