Tuesday, May 17, 2011

Highlights of Peterson's Calgary Speech April 29

http://www.box.net/shared/nr9jxt3s34

MYALGIC ENCEPHAMOLOMYELITIS/CHRONIC FATIGUE SYNDROME

THE RESEARCH FRONTIER

Highlights of Dr. Daniel Peterson's presentation to medical practitioners:
April 29, 2011, Calgary

By Anne-Marie Woynillowicz Kemp, B.A., Dip.T., M. Ed.

Dr. Peterson began his presentation by describing ME/CFS as a complex
scientific journey in research.  Viral infections, endotoxemia,
altered intestinal microflora, GI muscosal barrier dysfunction,
cytokines and inflammation including  low NK cell function, increased
activation markers, oxidative stress, and mitochondrial dysfunction
are  a few of the possible markers found in patients with ME.  There
are no diagnostic tests available, however, there are definitive
bio-markers for ME.
  Finding a diagnostic test is critical for the
validity of the condition and to stimulate more treatment research.

RECENT RESEARCH

Currently there is much exciting research being published including
the Schutzer et al. study that compared cerebrospinal fluid proteomes
to differentiate ME and Post Treatment Lyme Syndrome
(PTLS).  Patient
sets were 43 ME subjects that met the Fukuda Criteria, 25 subjects who
met the CDC  criteria for Lyme disease and had completed a minimum of
three weeks of IV antibiotic therapy at least four months earlier, and
11 healthy controls.  Using mass spectroscopy and liquid
chromatography, the research team generated a comprehensive list of 30
000 peptides in the sample pooled from the subjects in each disease
group. The results were as follows:

-738 proteins were found only in the ME subjects
-692 proteins were only found in PTLS samples
-724 proteins were only found in the normal controls.

Conclusions drawn from this study are that there are distinct sets of
proteins that can distinguish ME patients from PTLS patients and
normal controls.  PTLS patients also have a distinct profile. Proteins
relevant to specific neurological functions were lower in ME patients
indicating that the brain is not functioning properly and proteins
specific to immune function were markedly elevated.

Another study presented was the LEUKOTROPIC (living in white blood
cells) HERPES VIRUS IN PATIENTS WITH POST INFECTIOUS FATIGUE, Knox et
al., March 2011.  The goal of this study was identification of chronic
active herpes virus infections in individuals in order to prevent the
misdiagnosis of "ME/CFS" and thereby justify new intervention
strategies, such as antiviral therapy.  All subjects met the CDC
criteria for ME and had systemic signs and symptoms of an active,
ongoing infection. They also met the Canadian Consensus Criteria
(CCC), Carruthers et al., 2003, which Dr. Peterson stated should be
referred to as the "World Definition" for ME.

Below are the results of patients positive for the following:

HHV-6 (human herpes virus 6)             54/194    27.8%
HCMV  (human cytomegalovirus)        71/249     28.5%
EBV (Epstein Barr virus)                         79/153     51.6%

An association has been found between several critical human molecules
such as the thyroid peroxidase protein and leukotropic human herpes
viruses.  This suggests a mechanism for the commonly reported finding
of increased prevalence of autoantibodies in people with ME and
strengthens evidence that autoimmunity can be triggered by infection.
Furthermore, there is speculation that the immunosuppressive potential
of HHV-6 may synergistically enhance the reactivation and replication
of both CMV and EBV.  Dr. Peterson added that beta herpes viruses are
treatable.

ELEVATED LEVELS OF HHV-6 ANTIBODIES IN INDIVIDUALS WITH PSYCHIATRIC DISORDERS

HHV-6 antibodies in individuals with psychiatric disorders were
discussed, Yolken and Dickerson, March 2011.  This research showed
that individuals with established schizophrenia had elevated levels of
antibodies to HHV-6, which suggests schizophrenia can be treated with
antivirals.

CMX001-CIDOFOVIR PIM CONJUGATE is an antiviral drug in phase 3 trials.
By linking a lipid to the phosphonate group of cidofovir, a drug has
been formed which is able to cross the intestinal wall and penetrate
target cells before being cleaved to free the antiviral, cidofovir.
Improved potency has been demonstrated in preclinical studies.  In
cell culture assays, CMX001 is significantly more active than
cidofovir against double-stranded DNA viruses including:

-orthopox viruses (variola, monkepox, vaccinia, cowpox and ectromelia)
-herpes viruses (CMV, herpes simplex virus (HSV)-1,and 2, HHV6,-8,
varicella zoster virus(VZV), Epstein Barr virus (EBV)
-multiple adenoviruses.

Dr. Peterson suggested that CMX001 is an almost perfect drug as it
only needs to be administered orally 2 times a week.  This makes it
much more accessible than the current intravenous options for the
human herpes viruses.

APOPTOTIC SERUM DNA TESTING

Apoptosis is a natural process of self-destruction (programmed cell
death) in certain cells that is determined by the genes and can be
initiated by a stimulus or by removal of a repressor agent.  In March,
2011, Chronix Biomedical filed a provisional US patent application
jointly with Hemispherx Biopharma, Inc on a blood test for ME.
Chronix is developing disease-specific biomarkers based on DNA
fragments that are released into the bloodstream by damaged and
apoptotic cells.

The Chronix Biomedical blood test for ME is limited to investigational
use because it has not been evaluated by any regulatory agents yet. It
is expected that this test will be 100% accurate and that it will be
inexpensive.

XMRV

XMRV is proving to be highly controversial and is providing much
healthy debate and research.  Xenotropic viruses originate in mice but
can only infect cells from another species.  Most retroviruses,
especially members of the gamma retrovirus genus, can induce tumors as
a consequence of integrating their viral genome into the host cell
chromosome and activating proto-oncogenes (a normal gene that has the
potential to become an oncogene).

To date, there have been at least 21 studies of XMRV research in ME.
Two studies, Lombardi et al, October 2009 and Lo et al, September
2010, have supported XMRV in ME.  Nineteen studies have not found a
link to XMRV.  These include Erlwein et al., January 2011, Groom et
al., February 2010, Hong et al., September 2010, Heinrich et al.,
October 2010.

There are suggestions that some test kits were contaminated.

NEW RESEARCH DIRECTIONS FOR ME

Currently there are two large studies for ME. The first is at Columbia
University, headed by Dr. Ian Lipkin.  Dr. Lipkin is internationally
recognized for his work with SARS.  He is responsible for discovering
SARS and is credited with saving millions of lives, especially in
China.

The ME world is truly fortunate that Dr. Lipkin has agreed to do two
studies on ME.  Through viral assays for known and unknown pathogens,
Dr. Lipkin will be looking for all human viral pathogens.  As well,
there is a study of 240 post SARS patients from Toronto, Canada.
These patients are being tracked and approximately 6 to 8% developed
identical symptoms to ME.

Dr. Peterson is involved with the second large study which is being
conducted at Bond University, Gold Coast, Australia.  This research
study is looking at Natural Killer (NK) cell phenotype and functional
study.  Currently, the team is applying for permission to do spinal
fluid tap for a viral assay on ME to determine the cause of NK cell
dysfunction.
At this time, Dr. Peterson recommends measuring of NK function for diagnosis of ME as it is the most reliable marker for ME.

THE FUTURE

Significant strides are being made in research due to registries and
biobanking.   Nosology is the branch of medicine dealing with the
classification of diseases, which traditionally was built using signs
and symptoms.  Now, nosology can be based on gene expression and is
improved with clinical markers, lab markers and biotech markers.
Because all disease could be redefined from a molecular perspective,
patient outcomes will improve.

Translational medicine allows researchers and clinicians to work
together.  Future direction of the translational model will ensure
there is large scale clinical data gathering through multiple
international sites involving patient and provider.  It will allow
biospecimen collection with connection to a clinical database with RNA
expression, DNA sequencing as well as other molecular testing.  There
will be focus on chronic and syndromic diseases such as ME.

The future looks promising.


REFERENCES

Schutzer SE, Angel TE, Liu T, Schepmoes AA, Clauss TR, et al. (2011)
Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment
Lyme Disease from Chronic Fatigue Syndrome. PLoS ONE 6(2): e17287.
doi:10.1371/journal.pone.0017287

Knox K et al. Systemic Leukotropic Herpesvirus Infections and
Autoantibodies in Patients with Myalgic Encephalomyelitis-Chronic
Fatigue Syndrome. 7th International Conference on HHV-6 and 7. March
1, 2011. Reston, VA.

Yolken R, Dickerson F  Elevated Levels of HHV-6 Anitbodies in
Individuals with Psychiatric Disorders. 7th International Conference
on HHV-6 &7. March 2011. Reston, VA.

Shin, Clifford H. Absence of XMRV and other MLV-related viruses in
CFS. J. Virol.
Doi:10.1128/JVI.00693-11. Published online ahead of print on 4 May 2011.

Moldofsky H & Patcai J.  Chronic widespread musculoskeletal pain,
fatigue, depression and disordered sleep in chronic post-SARS
syndrome; a case-controlled study. BMC Neurol. March 24 2011;11:37.

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