Dr. Moskowitz, please give us a brief overview of your medical background and tell us about your current work with Genomed.
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).
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.
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.
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.
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.
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)?
Please see above. All a patient would have to do to get started is to contact me at email@example.com (all lower case) or go to our website at www.genomedics.com.
What traditional therapies are you most impressed with for treating autoimmune diseases? What are the best results you've seen?
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.
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.
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.
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?
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.
Anything else you'd like to add or elaborate on, on the topic of treating CFS and FM? Any final comments?
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.