Lynn,

I don't know if this post is out of the scope of this group but thought I
would send it in anyway (I am a patient and do not have any relationship
with the Genomed company). I am excited about the possibility that they may
be on to something (maybe not a cure, but symptom control). I was wondering
if anyone has tried an ACE or ARB and if it helped. Also wondering if
anyone has had their TNF-alpha level checked and the results (high, low,
normal).

Thanks,
Tom

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Treating Chronic Fatigue Syndrome and Fibromyalgia: Interview with David
Moskowitz, M.D.
ImmuneSupport.com

10-03-2003

ImmuneSupport.com: Dr. Moskowitz, please give us a brief overview of your
medical background and tell us about your current work with Genomed.
Dr. Moskowitz: I'm trained clinically as an adult nephrologist (kidney
doctor) and general internist. I graduated from Harvard Medical School in
1980 and trained at Barnes Hospital and Washington University Medical School
in St. Louis from 1980 to 1987. From 1987 until 1998, I was an assistant
professor at St. Louis University Medical School, with a lab and practice at
the St. Louis VA Medical Center. In 1998, I started my first biotechnology
company. Genomed [current affiliation] is my second.
I began studying the angiotensin I-converting enzyme or "ACE" gene ten years
ago, while still in academia. My lab found that over-activity of ACE was
responsible for kidney failure due to diabetes and high blood pressure. What
was surprising was that another 150 or so diseases seemed to be caused by
too much ACE activity.
Genomed is a disease management company, meaning that our business model is
to get paid for taking better care of patients. We use existing drugs,
especially generic drugs, whenever possible, because they're the ones which
have the most known about them, in terms of possible side effects.
Our approach is to attack diseases at their source, so as to achieve
regression ("cure"). It just so happens that ACE appears to be at the source
of virtually all common diseases except prostate cancer. In particular, all
autoimmune diseases, such as Lupus, Rheumatoid Arthritis, Multiple
Sclerosis, and even allergies to penicillin and sulfa drugs, start with
overactivity of ACE. The logical treatment to try, then, especially for
diseases with no good treatment yet, is an ACE inhibitor or an angiotensin
II blocker (ACE makes angiotensin II).
ImmuneSupport.com: You said that "to the extent Chronic Fatigue Syndrome
(CFS) and fibromyalgia (FM) are autoimmune diseases, I can treat them."
Please elaborate a bit on your belief that CFS and FM are autoimmune in
nature. As you know, debates about the true nature and pathology of these
diseases are ongoing.
Dr. Moskowitz: Because these are difficult diseases to diagnose and treat,
very little is known about them. For a long time patients who suffered from
CFS or FM were thought to be "making it up" or somatisizing psychiatric
issues. There is increasing recognition that FM and CFS may be autoimmune in
nature.
See, for example, the following reference:
Nippon Ika Daigaku Zasshi. 1999 Aug;66(4):239-44. [Autoimmune Fatigue
Syndrome and Fibromyalgia Syndrome][article in Japanese], Itoh Y, Igarashi
T, Tatsuma N, Imai T, Yoshida J, Tsuchiya M, Murakami M, Fukunaga Y.
Department of Pediatrics, Nippon Medical School, Tokyo, Japan. [Editor's
note: This abstract can be read on www.ImmuneSupport.com at
http://www.immunesupport.com/library/showarticle.cfm?id=5287&T=CFIDS_FM]
We have encountered two patients with fibromyalgia initially diagnosed as
having Autoimmune Fatigue Syndrome (AIFS). To investigate the relationship
between AIFS and FM, the distribution of the tender points in patients with
AIFS was assessed according to the ACR criteria for FM. It was revealed that
AIFS patients had 5.6 tender points on average. Patients with headaches,
digestive problems, or difficulty going to school had more tender points
than patients without. Patients with ana titers < 1:160 had more tender
points than patients with ana > or = 1:160. Anti-sa negative patients had
more tender points than positive patients.
These results suggest a relationship between AIFS and FM in terms of the
pathophysiologic mechanisms of the numerous tender points. In other words,
ana-positive FM patients could be one form of AIFS, as well as ana-positive
Chronic Fatigue Syndrome patients. Thus, autoimmunity could explain the
controversial disease entities of FM and/or CFS.
There is still much debate about this, since the antigen (viral or self)
hasn't been found for most patients.
But the symptoms of CFS and FM most resemble the flu, and suggest the work
of the monocyte/macrophage, a key player in the host's innate immune
response. Tumor necrosis factor-alpha (tnf-alpha, or cachectin) is just one
of many hormones released by activated macrophages. In fact, most of the
symptoms of the flu (muscle aches or "myalgias," weakness, fatigue) are due
to release of hormones from macrophages.
Since activated macrophages express ACE on their surface membrane, ACE has
something to do with their activated state. The product of ACE, angiotensin
II, is probably an activating hormone, or "cytokine," for macrophages.
Blocking the macrophage with an ACE inhibitor or angiotensin II receptor
blocker ("arb") is a very gentle, benign way of trying to tone down the
inflammation. We have seen it work for several diseases already
characterized by overly exuberant inflammation or even outright autoimmune
disease.
ImmuneSupport.com: What conditions that you have treated do you believe are
closely connected with CFS & FM? How do you go about effectively treating
those conditions/diseases? Please describe a typical standard treatment
protocol.
Dr. Moskowitz: So far, we've had small case series showing positive results
for the following diseases (in parentheses is the number of patients with
each disease):
Psoriasis (1 patient was able to stop taking 75 mg of methotrexate a day
when getting an adequate, tissue-inhibitory dose of an ACE inhibitor)
Alopecia areata (about 30 patients; hair loss was stopped abruptly--within
36 hours--in the first case, a 14 year old; since then about 30 people with
chronic alopecia--no hair for years or even decades--have taken an
angiotensin ii receptor blocker and are very slowly seeing regrowth of hair
they haven't seen for years).
West Nile Virus Encephalitis (9 patients; the only one not to respond
promptly--within 24 hrs on average--to treatment with an arb was a single
patient who also has chronic leukemia. In the other 8 patients, weakness,
fatigue, headache, mental confusion all disappeared within 12-36 hours).
Multiple Sclerosis (~6 patients: here the time scale of the illness is very
slow, and it will be another few years before we know whether our approach
is helping because the disease itself progresses so slowly).
What we would prescribe for a patient with CFS or FM would be the same as we
have been using for patients with alopecia areata or West Nile Virus
Encephalitis (and that we shall be using against SARS): an arb, at the
lowest dose, taken at bedtime so as to avoid dropping the blood pressure too
low. Prescribed this way, nobody has had to discontinue our treatment
because of dizziness or light-headedness due to too low a blood pressure.
ImmuneSupport.com: You mentioned that you do not currently have any CFS or
FM patients in your care. How would you propose treating a patient with CFS
or FM, or both (as overlap of the two conditions is common)?
Dr. Moskowitz: Please see above. All a patient would have to do to get
started is to contact me at dwmoskowitz@... (all lower case) or
go to our website at www.genomedics.com.
ImmuneSupport.com: What traditional therapies are you most impressed with
for treating autoimmune diseases? What are the best results you've seen?
Dr. Moskowitz: The only widely used treatment for autoimmune diseases like
Lupus or Rheumatoid Arthritis is systemic steroids (oral prednisone).
Unfortunately, they carry a 50% 5-year mortality rate, as well as hastening
osteoporosis and predisposing to diabetes and hypertension.
Other immunosuppressants, such as Cyclosporin, Imuran (azathioprine),
Cyclophosphamide (cytoxan), and Methotrexate are equally toxic, if not more
so. The latter drugs can depress the bone marrow for weeks on end.
Arb's (or ACE inhibitors, for people with high blood pressure) represent a
very benign form of immunosuppression, so benign that it will come as a
great surprise to everyone's physician that they are even capable of
immunosuppression at all.
ImmuneSupport.com: You mentioned your interest in a clinical trial for
treating CFS and FM patients. Please describe the trial you have in mind,
including what drugs or alternative therapies you would employ in such a
trial.
Dr. Moskowitz: As I mentioned above, all a patient has to do is contact me
by email. I would email back a description of the trial, and an informed
consent, for them to share with their physician. Their physician would have
to agree with the trial, since s/he will be prescribing the drug and
following the patient's blood pressure. I will then follow the patient by
email and once a month ask how they are feeling.
To do an unblinded, non-randomized, non-placebo controlled trial like this
is free, meaning that it will be done. To make it randomized or blinded or
placebo-controlled would greatly increase its cost, making it impossible to
do. Case series of consecutive patients tried on a particular treatment are
a time-honored method of testing out new treatment approaches, and will be
publishable. Clearly, the more patients in the case series who respond
positively, the more impressive the study. So we think we've found a way to
perform needed clinical trials in the absence of any external funding
whatsoever.
ImmuneSupport.com: Where else is your research taking you that is relevant
to CFS and FM patients and practitioners? Do you see any new drug targets on
the horizon that could be particularly exciting for these patients?
Dr. Moskowitz: I am reasonably confident that blocking angiotensin II will
make CFS and FM patients feel better. But they'll be on the right drug to
guard them against many other serious diseases. For example, I mentioned
that arbs (and ACE Inhibitors) are our choice to prevent death from West
Nile Virus Encephalitis and SARS. We also think they will delay or perhaps
even prevent most diseases of aging, including all cardiovascular disease
and most cancers other than prostate.
In the future, we would be delighted to get DNA samples from patients with
CFS and FM to look for additional disease-predisposition genes. But this
will require funding, which we currently don't have.
ImmuneSupport.com: Anything else you'd like to add or elaborate on, on the
topic of treating CFS and FM? Any final comments?
Dr. Moskowitz: I really appreciate your interest in our approach. The
rate-limiting step for all these trials is getting word out to the patients
who suffer from the diseases.
Here is what they send you:

Fibromyalgia and Chronic Fatigue Syndrome Clinical Trial

At GenoMed, a biotechnology company in St. Louis, Missouri, we recently
discovered that autoimmune diseases like rheumatoid arthritis may be caused
in part by over-activity of the angiotensin I-converting enzyme, which is
abbreviated as ACE. Fibromyalgia is a painful disease which is poorly
understood, but is likely to have an autoimmune component, since painful
muscles and joints are commonly seen during a body's immune response to
viruses, as in the "flu." Chronic fatigue syndrome (CFS), like fibromyalgia,
is characterized by flu-like symptoms that could arise from release of
signaling molecules from macrophages such as tumor necrosis factor
(TNF-alpha).

Activated macrophages and T cells express ACE on their surface membrane,
suggesting that ACE is important in stimulating the immune response. The
main product of ACE, called angiotensin II, is therefore likely to be a
signaling molecule for immune cells, in other words, a "cytokine."

What's nice about finding that other autoimmune diseases may be caused by
too much ACE activity is that safe, relatively inexpensive drugs to inhibit
ACE activity already exist. ACE inhibitors have been safely used for a
completely different disease, high blood pressure, for over 20 years.
Hundreds of millions of patient-years' experience has been accumulated with
this class of drugs. The only common side effects are a dry cough in up to
10% of patients, and swollen lips ("angioedema") in 1% of patients. The
first ACE inhibitor, captopril, has a reactive sulfur atom, and was
associated with bone marrow suppression in 1 in 10,000 patients. Newer ACE
inhibitors cannot bind covalently to proteins like captopril, and have not
been associated with this last side effect, called "granulocytopenia."

A related class of drugs, the angiotensin II receptor blockers (ARB's), have
been used for a decade, and have even fewer side effects than ACE
inhibitors. For example, cough is very rare, and angioedema is even rarer.
No cases of bone marrow suppression have yet been seen. What's more, small
doses of an ARB can be used in patients whose blood pressure is normal or
even low without causing any further lowering of the blood pressure and
dizziness.

We would like to work through your own physician. Informed consent will be
required, as well as keeping us updated from time to time about how you're
doing. Your outcome, along with that of other patients with fibromyalgia or
CFS taking an ARB or an ACE inhibitor, will be reported in a peer-reviewed
journal. Of course, no personal identifier will be included.

Sincerely yours,

Dave Moskowitz MD FACP
Chairman and Chief Medical Officer
GenoMed, Inc.
909 S. Taylor Ave.
St. Louis, MO 63110
Tel. 314-977-0110
dwmoskowitz@...