Title: Detection of Microorganisms in Specimens from
Patients with Multiple Sclerosis and Other Autoimmune Diseases
Patients with Multiple Sclerosis and Other Autoimmune Diseases
IRB Protocol #00047316
March 19, 2012
This proposal aims to identify a specific cause of multiple sclerosis (MS) in response to the NMSS request for applications entitled, “The search for the cause or trigger of MS.” MS is a chronic demyelinating disease of unknown cause that affects the brain and spinal cord of about 400,000 individuals in the U.S. Viruses have long been suspected as causative agents in MS due to observed geographic patterns of disease, isolated outbreaks, and migration studies. Numerous viral infections of the central nervous system can lead to demyelination, including distemper (dogs), measles (humans), and influenza (humans). Our group proposes a search for a viral cause or trigger of MS using molecular techniques. Novel unculturable viruses that cause human disease continue to be discovered using molecular techniques including hepatitis C (1991), corona virus NL63 (2004), bocavirus (2005), and rhinovirus C group (2007). New human polyoma and arenaviruses were recently identified as causes of human diseases by a technique called, “deep sequencing.”
Our group has performed deep sequencing on frozen, preserved, brain samples from deceased MS patients and normal controls. High-throughput or deep sequencing was used to specifically identify millions of RNA fragments in each of these human brain specimens. A public database of viral sequences (GenBank) was then used to analyze the resulting RNA sequences. The computer program “MegaBLAST” was used to determine which brain sequences matched known viral sequences. Another program developed by our group was used to compare each MS brain specimen with a set of normal brain specimens. We used these sequences to demonstrate the presence of hepatitis G virus (GBV-C) in one of the MS brain specimens. In preparation for this proposal, our lab has shown that deep sequencing can also be performed on fixed, paraffinized tissue — the form used to study and preserve brain tissue after a brain biopsy has been performed. Based on these results, we propose using deep sequencing to identify viral candidates in the brain tissue. Follow up techniques will be used to confirm or refute the presence of specific viruses in each brain specimen.
This new proposal employs deep sequencing to search for viral RNA sequences within biopsied brain tissue obtained from living patients who have experienced acute demyelination. Most of these persons already have, or will develop, MS. The investigators have brain tissue from 5 such subjects in addition to spinal fluid and blood from 11 others. About 30 additional research subjects are available through a new collaboration with a neuropathologist. Sequences from these diseased specimens will be compared to sequences taken from a similar number of control brain specimens. Any candidate viruses that emerge from this work will be studied by using the blood and CSF taken from other patients with acute demyelination.
This work complements – and brings into the realm of the living – the ongoing sequencing efforts by our group among deceased subjects with primary progressive MS, currently funded by the NINDS. The investigators believe that this new technology – deep sequencing – is ready for the application to this very difficult problem and that patients with acute demyelination represent a unique opportunity to identify one or more viral infections that trigger MS.
Who: Persons who
have experienced any form of acute multiple sclerosis (MS), including “Marburg
variant MS” and “tumefactive MS”, disseminated encephalomyelitis (ADEM), optic
neuritis, clinically isolated syndrome (CIS), or another demyelinating disease
who have had a brain biopsy may be eligible to enter this phase of the project. Prospective subjects may be identified by
authorized persons affiliated with the above study who have completed CITI
training and any other training required by the IRB. Administration of informed consent will be
performed only by the P.I. (Dr. Kriesel) or his designated study coordinator
(currently Amiteshwar Bhatia). Subjects
may be recruited worldwide.
have experienced any form of acute multiple sclerosis (MS), including “Marburg
variant MS” and “tumefactive MS”, disseminated encephalomyelitis (ADEM), optic
neuritis, clinically isolated syndrome (CIS), or another demyelinating disease
who have had a brain biopsy may be eligible to enter this phase of the project. Prospective subjects may be identified by
authorized persons affiliated with the above study who have completed CITI
training and any other training required by the IRB. Administration of informed consent will be
performed only by the P.I. (Dr. Kriesel) or his designated study coordinator
(currently Amiteshwar Bhatia). Subjects
may be recruited worldwide.
What: The
following text is designated as a guide to find prospective subjects using the
wordwide web (internet). Authorized
study staff will use this language to initiate conversations with prospective
subjects or their representatives via the web, through email, on the telephone,
or in person. Any resulting discussions
will follow the boundaries of the study set by the IRB approval documents. The P.I. will supervise this process and get
directly involved as necessary. Proposed
text:
following text is designated as a guide to find prospective subjects using the
wordwide web (internet). Authorized
study staff will use this language to initiate conversations with prospective
subjects or their representatives via the web, through email, on the telephone,
or in person. Any resulting discussions
will follow the boundaries of the study set by the IRB approval documents. The P.I. will supervise this process and get
directly involved as necessary. Proposed
text:
Our research group is interested in infections that might cause some
cases of multiple sclerosis (MS). We
believe our best chance to “catch a
virus in the act” is obtain existing brain biopsy tissue from persons who have
or had an acute demyelinating disease, including multiple
sclerosis, acute disseminated encephalomyelitis, optic neuritis, and clinically
isolated syndrome. Our group would like
to collect and study leftover brain tissue, including fixed and paraffinized
tissue, from patients with demyelinating diseases. We do not want to collect new specimens, but rather
wish to collect existing brain biopsy tissue (stored in a hospital pathology
department) that has already been examined.
No visits to the University of Utah Hospital
are needed. Informed consent for participation is
required; this can be done on the phone and by mail. Clinical information relevant to the study
may be collected over the phone, by email, or through other electronic methods. Brain tissue samples may be subjected to new
techniques that may identify microbes (bacteria or viruses). To avoid any confusion or false hopes, the
results of this testing are to be reported only through a treating
physician. This is academic research
which is voluntary and not for profit, approved and supervised by the
University of Utah Institutional Review Board. No compensation will be provided.
cases of multiple sclerosis (MS). We
believe our best chance to “catch a
virus in the act” is obtain existing brain biopsy tissue from persons who have
or had an acute demyelinating disease, including multiple
sclerosis, acute disseminated encephalomyelitis, optic neuritis, and clinically
isolated syndrome. Our group would like
to collect and study leftover brain tissue, including fixed and paraffinized
tissue, from patients with demyelinating diseases. We do not want to collect new specimens, but rather
wish to collect existing brain biopsy tissue (stored in a hospital pathology
department) that has already been examined.
No visits to the University of Utah Hospital
are needed. Informed consent for participation is
required; this can be done on the phone and by mail. Clinical information relevant to the study
may be collected over the phone, by email, or through other electronic methods. Brain tissue samples may be subjected to new
techniques that may identify microbes (bacteria or viruses). To avoid any confusion or false hopes, the
results of this testing are to be reported only through a treating
physician. This is academic research
which is voluntary and not for profit, approved and supervised by the
University of Utah Institutional Review Board. No compensation will be provided.
If
you or someone you know has or had a demyelinating disease and
a brain biopsy please call 801-587-3831 or contact the investigator, Dr. John
Kriesel by email at [email protected], or U.S. mail at the University of Utah School of Medicine, 30 N 1900
E, Room 4B-322, Salt lake City, Utah 84132.
you or someone you know has or had a demyelinating disease and
a brain biopsy please call 801-587-3831 or contact the investigator, Dr. John
Kriesel by email at [email protected], or U.S. mail at the University of Utah School of Medicine, 30 N 1900
E, Room 4B-322, Salt lake City, Utah 84132.
The information posted on this site is consistent with the research reviewed
and approved by the University of Utah Institutional Review Board (IRB). However, the IRB has not reviewed all material
posted on this site. Contact the IRB if
you have questions regarding your rights as a research participant. Also contact the IRB if you have questions,
complaints, or concerns which you do not feel you can discuss with the
investigator. The University of Utah IRB
may be reached by phone at (801) 581-3655 or by e-mail at [email protected].
and approved by the University of Utah Institutional Review Board (IRB). However, the IRB has not reviewed all material
posted on this site. Contact the IRB if
you have questions regarding your rights as a research participant. Also contact the IRB if you have questions,
complaints, or concerns which you do not feel you can discuss with the
investigator. The University of Utah IRB
may be reached by phone at (801) 581-3655 or by e-mail at [email protected].
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