Wednesday, June 16, 2010

Pick up those pens!

Please write Dr. Francis Collins of the NIH and ask him to fund important biomedical research into Neuroimmune Disease Research.

http://energycommerce.house.gov/index.php?option=com_content&view=article&id=2042:hearing-on-nih-in-the-21st-century-the-directors-perspective&catid=132:subcommittee-on-health&Itemid=72
 
 
* * *
The WPI is doing an admirable job of fundraising (have you reserved your tickets for I Hope You Dance in September?  or made your $10 pledge?), but NIH has more money available than WPI can raise. 
 
Now that we have XMRV to hang our hats on, let's get it investigated -- at government expense, not with pennies scrounged by impoverished patients! -- and see how quickly they can get a valid treatment for us.  (Pacing is not a treatment!  It keeps us from declining but doesn't get us back to full health.)
 
Yes, I know, some patients are using AIDS drugs as a stopgap, but I've heard from other reputable sources that those drugs are highly toxic and CFS patients shouldn't go near them.  Personally, I'm feeling well enough right now that I *do* have something to lose and don't want to take that chance; there have been times in the past that I was sick enough to not care about such things because I was half-dead anyway.
 
Dr. Murphree (www.DrRodger.com) had told me that it takes a minimum of one year of good sleep to make up for each year of bad sleep, and 2010 is the year that he predicted was the earliest that I would reach maximum improvement (though it can go up from here, since he did say "minimum of" and not "exactly one-to-one").  If this is where I'm stuck the rest of my life, I can be happy; I'm functional enough to survive.  Would I prefer to improve further?  Absolutely.  I'd love to get back to work full-time.

 
 
 

Tuesday, June 15, 2010

Support WPI with a click

 http://apps.facebook.com/chasecommunitygiving/rules

It's time for Chase Community Giving on Facebook :) please vote for Whittemore Peterson Institute for Neuroimmune Diseases!!!  http://www.chasegiving.tk/
 

 

Monday, June 14, 2010

The Whittemore Peterson Institute: Building Bridges through Private and Public

 
The Whittemore Peterson Institute: Building Bridges through Private
and Public Sector Collaboration
Mol Interv June 2010 10:120-126; doi:10.1124/mi.10.3.1

http://molinterv.aspetjournals.org/content/10/3/120.full


Annette Whittemore

The Whittemore Peterson Institute's (WPI) publication of its
ground-breaking study on October 8, 2009, of the link between a
cancer-related retrovirus, XMRV, and patients with myalgic
encephalomyelitis/chronic fatigue syndrome ("ME/CFS") brings a
desperately needed legitimacy to a complex yet controversial and
misunderstood disease (1). News of this significant association
brought hope to millions around the world who have suffered in silence
from its devastating effects. Perhaps, just as important, the
discovery of XMRV infection in humans allows the medical world to
construct a testable hypothesis of how XMRV may cause or contribute to
illnesses across a wide spectrum of chronic inflammatory diseases and
cancers and new paradigms of treatment and perhaps prevention.

That the discovery happened in just three years of a small research
institute's existence is almost as amazing as the extraordinary
scientific work.
This is the story of how and why the Whittemore
Peterson Institute came to be. It is a story of multiple
collaborations at every level, revealing a blueprint for other groups
of dedicated scientists, doctors, and philanthropists to create
greater progress through unique and selfless partnerships across
nontraditional boundaries. Like other philanthropic endeavors, it
began as an idea evidenced through personal suffering and acted upon
after all other avenues had failed.

The personal decision to commit time and money to build an institute
for patients with neuroimmune diseases came from a desperate need for
medical solutions to a disease that had been destroying our daughter's
life for over twenty years. We were also faced with the reality that
experienced physicians were retiring without passing on their
knowledge of ME/CFS to new physicians . In addition, the existing
medical establishment lacked both knowledge and medical tools to
effectively treat patients who suffered the debilitating effects of
this neurological disease. Around the world, those who suffer with
ME/CFS have been told that their physical disorder is a manifestation
of a psychiatric disease. Subsequently, these patients may then be
denied medical support by their government-run health care programs.

Box 1. The Historical Description of Myalgic Encephalomyelitis

Myalgic Encephalomyelitis was first described by Melvin Ramsey in the
UK after an outbreak in the 1950s [(5–7), see also (8)]. He coined the
term to describe the muscle pain and symptoms of brain and spinal-cord
inflammation its sufferers experienced. In the early 1980s, an
outbreak in the United States of a disease with the identical symptoms
of ME was reported to the CDC. With little input from the physicians
who first described the disease, a small group of scientists, doctors
and psychiatrists renamed the disease from the earlier term, chronic
Epstein-Barr virus, to simply "Chronic Fatigue Syndrome" (9). By
emphasizing fatigue as a symptom, which is known to be associated with
many chronic conditions, those with "CFS" quickly became confused with
others who were simply "tired" or "burned out" from overwork.
Unfortunately for those who were truly ill, and not merely tired, this
misunderstanding has prejudiced scientists and doctors before they
ever examined a patient with "CFS."

Journey Through A Medical Wilderness

Our odyssey began in 1989, when my daughter, Andrea, became ill with a
mononucleosis-like illness and then failed to return to normal health
After many months of continuous relapsing and remitting flu-like
symptoms, she was referred to a major medical institution for
evaluation. She was given a cursory check up, then provided with a
psychological explanation for her infectious symptoms of sore throat,
severe head and nerve pain, swollen lymph glands, night sweats,
tachycardia, and muscle aching fatigue. Even to a non-scientist that
answer seemed ridiculous. The consulting physicians could offer no
explanation for what was clearly a biological phenomenon.

I returned home with Andrea, determined to find a doctor who knew
something about the outbreak of a disease that had occurred at Lake
Tahoe, a favorite summer destination frequented by our family. A
physician and next door neighbor, Reggie Davis, who had known Andrea
as a healthy child and saw her frequently during her illness, was
convinced that her symptoms were like those of individuals from that
outbreak. He suggested that we see Raymond Scott, an internist in
Reno, even though Andrea was only twelve. Before allowing her to see
the doctor, I scheduled an interview with him to be sure he knew
something about the disease: I was not going to allow her to be told
that her symptoms were not real, as did the doctor who told her that
she "most likely hated her parents, her friends, and her school."
Through it all, other physicians confirmed what I knew––that my
daughter was ill with a very real disease. Fortunately, Dr. Scott had
worked with other patients in the Incline Village, Lake Tahoe area and
knew more about CFS than any other doctor in Reno. Although the
treatments he offered provided only symptomatic relief, her life
improved under his compassionate care. She continued this modest
improvement until she decided to enroll at the University of
Nevada–Reno. The admission policy required the measles, mumps, and
rubella (MMR) vaccination prior to starting classes. Within five days
of the MMR vaccination, Andrea had a severe relapse and never regained
her previous level of health.

Reflections

As her health continued to deteriorate, Dr. Scott became more
concerned. Soon we were on our way to another major medical
institution in California, where rounds of tests and several
physicians later, we ended the visit with a referral to another
hospital's pain clinic where she was told she should fill out a
questionnaire everyday, then learn to live with her pain. Just
eighteen years old, Andrea was facing a lifetime of pain that was so
severe she required the use of a transcutaneous electrical nerve
stimulation unit and injections to make it through the day.

Only after a visit to a local gastroenterologist, one year later, did
we find that much of her pain arose from a diseased gallbladder.
Within six months of her gallbladder surgery, she also had to have her
appendix removed. We began to worry that a vital organ might soon be
affected, so we followed her doctor's advice and sought out internist
Daniel Peterson of Incline Village. Months later, Andrea was accepted
into his practice.

Dr. Peterson has a passion for his work and his patients. He is one of
a small number of well-respected CFS physicians and was one of two
doctors who first alerted the Centers for Disease Control to a
possible outbreak of a new disease, then dubbed chronic Epstein-Barr
virus (EBV) (2). Dr. Peterson knew that something was making his
patients sick and keeping them from getting well again. The CDC's
quick reply left Peterson with the impression that the CDC didn't know
what the cause was and that it did not think it warranted more
attention. Without serious government-backed follow-up to validate
those initial and unfortunate faulty conclusions, medical scientists
were dissuaded from researching the cause of the new disease, while
many more around the world became ill.

Patients who had what was now known as ME/CFS were left with modest
victories to cheer and little medical hope. In 1993, Nevada became one
of the first states to request that the President and Congress
increase funding for research into CFS4. In addition, the Nevada
legislature agreed to include the drug, Ampligen, which acts to
stimulate the body's antiviral defenses, in modest recovery models for
Phase III trials. Treadmill VO2max (i.e., the volume of oxygen
utilized during exercise of maximum exertion) was used as a guide to
evaluate patient disability and response to treatment. When Andrea
turned twenty-one, she enrolled in the phase III drug trial. Twice a
week she was given an intravenous (iv) infusion that at first caused
her to experience a worsening of her symptoms. Other days, she spent
hours receiving nutrient iv fluids that supported her health. Finally,
after one year of treatment, she began to improve with the drug and
continued to take it, off and on, for eight years.

Blood tests, developed in a laboratory in Belgium, helped determine
some of the unique traits found in many CFS patients. After the
bombing of the World Trade Center, however, transporting blood
overseas was no longer an option. We and a few other patient advocates
were approached by one of the owners of the Belgium lab and asked to
support the establishment of a US lab that would perform the same
tests. Because most of the American patients lacked the insurance to
pay for the tests, my husband, Harvey, and I agreed to help and soon
supported the lab in its entirety. We felt supporting this lab was
critical to the ongoing work in developing and testing therapies for
patients with CFS. As a result of supporting the lab, valuable RNase L
studies and natural killer (NK) cell work were able to continue, which
eventually led to the hypothesis that patients with CFS might be
infected with xenotropic murine leukemia virus-related virus (XMRV).
While taking Ampligen, Andrea improved to 75% of her previous levels
of energy and stamina, but despite many of the positive outcomes, she
continued to fall ill with opportunistic infections. For unknown
reasons, Andrea began to develop reactions to Ampligen, making her too
sick to continue. Once off the drug, she began a continuous decline.
Today, without treatment she experiences daily seizures, nausea,
vomiting, severe allergies, and painful lymph-node swelling. As a
result, she requires nearly full-time help to care for herself and her
home. Instead of answers and solutions, we were left with
hopelessness.

CFS: Challenges To Overcome

The difference between the actual effects of this disease and that
which is portrayed in the popular media could not be greater. The
current CDC definition states that a patient must satisfy two
criteria:

1. Have severe chronic fatigue of six months or longer duration, with
other known medical conditions excluded by clinical diagnosis; and

2. Concurrently have four or more of the following symptoms:
substantial impairment in short-term memory or concentration; sore
throat; tender lymph nodes; muscle pain; multi-joint pain without
swelling or redness; headaches of a new type, pattern or severity;
unrefreshing sleep; and post-exertional malaise lasting more than
twenty-four hours.

The symptoms must have persisted or recurred during six or more
consecutive months of illness and must not have predated the fatigue.
The CDC then recommends a series of common blood tests, but goes on to
predict that:

"More than 90% of patients presenting with severe fatigue will test at
normal levels for the series of laboratory tests listed above.
Assuming that there is nothing in the physical examination or in the
personal history of the patient that suggests a clear direction to the
doctor, no further laboratory testing is recommended."

With what other disease could government health officials suggest
waiting six months for a diagnosis, using tests that will only tell
you what it is not, and leave you with no answers as to what it is or
how to treat it?
The CDC concludes that because not every CFS patient
has the same abnormalities in their immune systems or brain scans,
further evaluation is not necessary. Thus, scientific answers become
even harder to obtain.

Perhaps what is missing most from the public's awareness is the
description of the most severely ill patients, like Andrea, who, at
times, was so ill and weak that she was unable to feed herself or walk
unaided. As these patients' immune systems weaken and various chronic
infections take hold, they live their lives between doctor's offices
and their homes physically and emotionally isolated from their
families, friends, and communities. Many go on to develop
life-threatening complications. In a retrospective analysis, Leonard
Jason found that those diagnosed with ME/CFS died of heart disease,
cancer, or suicide at ages approximately twenty-five years younger
than the normal population. Only detailed epidemiological studies will
reveal the true complications of long term disease and mortality
resulting from the complications of this disease.

The problems that patients experience when dealing with the healthcare
system can be as difficult as the disease itself. Most doctors have
difficulty diagnosing ME/CFS and when they do, are at a loss as to
what to do for their patients. The lack of medical consensus is so
great that most doctors disagree on the best treatment strategies or
what, if any, biological treatments to consider. Doctors and patients
are left to their own devices, experimenting with drug treatments that
are unproven, toxic, or both. Scientific and educational information
surrounding ME/CFS is conflicting and often consists of anecdotal
observations from physicians. Additionally, many patients are told
they suffer from "faulty thinking" about the illness and are then
prescribed cognitive behavioral therapy and graded exercise therapy.

More Than A Foundation

It was evident to me, after working with another research foundation
to study CFS, that engaging various scientists to do related research
projects was only one part of the solution to the much bigger issues
surrounding ME/CFS. This initial research program was narrowly focused
on one virus and relied on individual researchers to apply for grants.
Much like the extramural grants of the NIH, these projects are
scattered among different unrelated researchers and not organized in a
comprehensive and coordinated manner.

One thing that I admired about the foundation's director was her
ability to access researchers to do the work that she felt might
reveal new information. After reading about the XMRV finding in
prostate cancer, I tried to contact the group of researchers at UCSF
that had made the extraordinary new discovery. I wanted to pay them to
test CFS patient samples using their viral-chip technology. After
several attempts, I gave up that effort and instead began to develop
another plan of action. That plan was to create a research program
within the structure of a medical research center.

Many advocacy organizations had expressed an interest in government
support of Centers of Excellence for the treatment of patients with
ME/CFS. In fact, to address the issues of CFS, a bench-to-bedside
approach was needed, requiring nothing less than an expert
institution, which would combine translational research with patient
diagnostics, treatments, and medical training for new doctors. When it
became apparent that no one else was willing to create such a center,
with the strong encouragement of my husband, family, friends, and
political leaders.

Reflections

I agreed to act. With a promise from medical doctors to support our
efforts, I committed my time and my family's resources to create and
build such an institute. In early 2005, Dr. Peterson and I began
working to describe this institute's future clinical practice.
Meanwhile, my husband discussed with John Lilley, then president of
the University of Nevada–Reno, the School of Medicine's desire for a
new medical research building. Our Governor and good friend, Kenny
Guinn, agreed to place this project in his state budget. Legislative
leaders who understood the potential benefits to both patients and
future medical education in this state also began to offer their
support. This new research facility was to house three significant
interest groups: researchers from the University of Nevada's Medical
School; the Nevada Cancer Institute; and the Center for Neuroimmune
Disease (now called the WPI). That winter, I gathered scientific
information for a presentation to the 2005 state legislature, arguing
the need for such a medical center. University representatives and
Nevada Cancer Institute scientists did the same. Passionate pleas were
made by several patient advocates in addition to our testimony. By the
end of the legislative session, ten million dollars has been allocated
to support a new research and medical office building5 (Figure 2). The
main portion of the building was built from bond money which was based
on the indirect costs of the researchers' grants. My husband and I
committed to give or raise an additional $5 million towards WPI's
portion of the building, and soon the construction began, bringing
reality to a dream.

The Real Work Begins

Judy Mikovits and I met at an HHV-6 Foundation conference in the
spring of 2006. It was at that conference that Dr. Peterson presented
patient data describing many longstanding CFS patients who had
developed rare lymphomas. Dr. Mikovits was intrigued and, as a
seasoned scientist with experiences in retrovirology, recognized a
potential for discovering a new disease-causing pathogen.
Shortly
thereafter, I asked Dr. Mikovits to serve as the Institute's full-time
Research Director. She immediately planned a comprehensive research
program to answer questions that would support the development of
diagnostics to help define those who had this illness. She began by
building a repository of patient samples and organizing her studies to
generate sufficient data to justify an NIH grant, which was submitted
in June, 2007 and finally funded in October, 2009.

Having the support of University leadership––President Milton Glick
and Ole Theinhaus, Dean of the Medical School––was also critical to
our success. Experienced scientists such as Steven St. Jeor, a CMV
researcher; Greg Pari, an expert in Kaposi's sarcoma-associated
herpesvirus (KSHV); and Ian Buxton, a pharmacologist, offered their
assistance. Soon after moving to the University, we organized a small
conference as a means to formally introduce ourselves. Researchers
from the University, the National Cancer Institute, and the WPI came
together with ME/CFS physicians, to discuss their areas of expertise.
The following year Dr. Mikovits led the first meeting of the
Institute's new scientific advisory board. Today, the WPI Scientific
Advisory Board engages scientists with expertise in cancer, infectious
disease, autoimmune diseases, immunology, and virology.

WPI has had to use a combination of funding mechanisms to pay for the
many different activities neccessary for the creation of a working
institute. Like many medical research non-profits, WPI must rely on
the talents of its researchers to receive grant support and the
ability of its administrators to raise funds from the larger
community. When a disease is not well understood and often maligned,
it is an even more daunting task. For example, it took WPI three years
to receive NIH funding for reasons unrelated to the quality of the
proposal.

Donations to the Institute come in many forms. WPI has a yearly gala
dinner which raises hundreds of thousands of dollars. We ask private
foundations, companies, and individuals for their help in a variety of
ways. We have also used yearend gift appeals and a new Facebook Cause
page to raise money and awareness. The WPI Web site has been a source
of donations, as well. The urgent need for a continuous source of
income to support the clinical work of the Institute is now our
greatest priority.

Generous patients, hopeful for answers, make up a significant part of
the funding in this disease. They must choose between several
organizations who claim to be doing important research work. It is
difficult for most laymen to decipher the kind of science they are
funding or whether or not the scientists are qualified to do the work.
Thus, private donations which are very competitive can be spent on
research that does not provide significant results. Educating the
public about the importance of our organization's own research
capabilities is time consuming and requires a full time effort, but is
extremely necessary if one is to gain public support.

The Intramural NCI Program: The Value Of Basic Research

The selection of Dr. Mikovits as the research director of the WPI was
fortuitous in that she had worked for twenty years in the Intramural
Program for the NCI as research technician, graduate student,
postdoctoral fellow and finally as head of the NCI contractor's lab of
Antiviral Drug Mechanisms. The NCI's tumor virus program of the late
1970s supported the identification of retroviral oncogenes in human
tissue and of the tumor-causing human retrovirus, human T cell
leukemialymphoma virus type I (HTLV-I) by Bernie Poiesz and Frank
Ruscetti, in the laboratory of Bob Gallo. By 1984, NCI investigators
were co-discoverers of a new retrovirus, HIV-1, which is the causative
agent of AIDS. It was natural for Dr. Mikovits to enlist the help of
her former NCI colleagues, Frank and Sandy Ruscetti, Mike Dean and
Rachel Bagni, to look for an infectious agent. Thus, NCI's investment
in funding basic research in animal and human virology made the
discovery process possible. Initially, the discovery process focused
on the use of a viruschip assay similar to the one used to discover
xenotropic murine leukemia virus-related virus (XMRV) in the tissue of
men carrying RNase L mutations who had prostate cancer (4). After two
and a half years of trying to make sense of the viral chip data, we
narrowed our focus to XMRV, because many CFS patients also suffer from
an RNase L defect, and initiated a collaboration with Bob Silverman, a
co-discoverer of the virus, of the Cleveland Clinic. All patient
material used in this study were subjected to four separate XMRV
assays: DNA PCR from peripheral blood cells (PBMC); viral protein
expression in PBMC; presence of antibodies in plasma; and the recovery
of infectious virus from plasma transmitted to indicator permissive
cell lines. After five months of a rigorous review process, the
journal Science published our findings (1).

The Aftermath: Still Stuck In Osler's Web

By attempting to bring chronic fatigue syndrome (CFS) research out of
the shadows and squarely onto the nation's health agenda, we knew that
we would be the object of much criticism from both the medical
establishment and those individuals invested in other theories of
disease causation. Previous experiences had shown that some of these
activities would parallel what happened during the early days after
the discovery of HIV and AIDS.

CFS was belatedly recognized as a legitimate disease entity by the
Centers for Disease Control in 1997 but is still denied recognition as
an infectious immune disorder.
The HHV6 foundation believes that HHV6
is the sole cause of CFS. A major CFS patient advocacy organization is
on record, having concluded that a retrovirus has nothing to do with
the pathophysiology of CFS. Much of the opposition outside of the CFS
community firmly believes this disease and others that are similar
arise from psychiatric disturbances.
Within a week of the Science
online publication, several scientists publicly announced that they
would not be able to replicate the findings, negative findings were
reported on blogs, and within a month, three negative papers had been
written and submitted about the lack of XMRV in CFS.

Without directed research allocations from a Director of an NIH
institute, it can take between three to five years before money can be
allocated to study the role of XMRV in disease. Fortunately, Robert
Wiltrout, Director of the National Cancer Institute's Intramural
Center for Cancer Research, has already requested that the scientists
in the intramural program begin to develop reagents to determine the
role of XMRV in the development of cancer and other chronic diseases.
The other difficulties surrounding funding of governmental research
grants are numerous, including the time it takes for the entire
process to be completed. NCI has developed a mechanism to rapidly give
new research funding to existing cancer centers. Unfortunately, when a
new, non-traditional entity such as the WPI is created, it must often
delay work until the funding is already in place. To solve these
problems, we have found it beneficial to work with other institutions
and experienced investigators who have offered to co-author grants in
a mentoring relationship. But we have also learned a valuable lesson:
a non-traditional entity may point out a new research direction, but
it must be confirmed by traditional engrained mechanisms.

Reflections

Although the challenges have been significant, the personal rewards
one receives by helping others through the work of this institute have
been tremendous. We meet and talk often with hundreds of individuals
who are thankful that the WPI is creating a scientific program of
discovery that will improve their lives. They have spent too many
years suffering in silence, often opting out of the medical world when
they can't find relief. Scientific efforts to solve the many questions
surrounding neuroimmune diseases have brought a renewed interest in
the field and hope to millions throughout the world. Below are just
two of thousands of messages sent to our offices. "Canada cheered when
we heard the news." Another patient wrote, "I do not have words to
thank you for the work you have done. It has now been 30 years since I
fell ill and I truly never thought I would see the day this terrible
knot was untied." Therein lies the motivation, despite all obstacles,
to continue this vital mission.


References
1. Lombardi VC, Ruscetti FW, Das Gupta J, Pfost MA, Hagen KS, Peterson
DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, et al. (2009)
Detection of an infectious retrovirus, XMRV, in blood cells of
patients with Chronic Fatigue Syndrome. Science 326:585-589.
2. Holmes GP, Kaplan JE, Stewart JA, Hunt B, Pinsky PF, and
Schonberger LB (1987) A cluster of patients with a chronic
mononucleosis-like syndrome. JAMA 257:2297–2302.
3. Jason LA, Corradi K, Gress S, Williams S, and Torres-Harding S
(2006) Causes of death among patients with chronic fatigue syndrome.
Health Care Women Int. 27:615–626.
4. Urisman A, Molinaro RJ, Fischer N, Plummer SJ, Casey G, Klein EA,
Malathi K, Magi-Galluzzi C, Tubbs RR, Ganem D, et al. (2006)
Identification of a novel gammaretrovirus in prostate tumors of
patients homozygous for R462Q RNASEL variant. PLoS Pathogens 2:e25.
5. Ramsay AM and O'Sullivan E (1956) Encephalomyelitis simulating
poliomyelitis. Lancet 270:761–764.
6. Ramsay AM (1957) Encephalomyelitis simulating poliomyelitis. Public
Health 71:98–112.
7. Ramsay AM (1957) Encephalomyelitis in north west London; an endemic
infection simulating poliomyelitis and hysteria. Lancet 273:1196–1200.
8. Ramsay AM (1986) Myalgic Encephalomyelitis: A baffling syndrome
with a tragic aftermath. M.E. Association Journal 1986, UK.
9. Jason LA, Najar N, Porter N, and Reh C (2009) Evaluating the
Centers for Disease Control's empirical chronic fatigue syndrome case
definition. J. Disability Policy Studies 20:93–100.

Medicine is not "a noble profession"

"Is medicine a noble profession?" Dr. Sanjay Gupta asked Dr. Jack Kevorkian in a recent interview. The answer: "No, it is not." Kevorkian, who served prison time for assisting in suicides, still stands by the practice. FULL STORY