GenoMed Reaffirms Potential Utility of Sartans for SARS
ST. LOUIS, April 28 /PRNewswire-FirstCall/ -- GenoMed, Inc (OTC Pink Sheets: GMED)("the Company" or "GenoMed"), a St. Louis, Missouri-based medical genomics and Next Generation Disease Management(TM) company, announced today that, after review of the available literature, it has changed its idea of mechanism but retains its conclusion that angiotensin II receptor blockers (ARBs), whose chemical names all end in "sartan," ought to be a valuable treatment for SARS (severe acute respiratory syndrome). The Company is still looking for patient and physician collaborators.
In its press release of April 25th, the Company discussed the utility of ARBs for T cell-mediated immunity, so-called "acquired immunity." But review of the lung pathology of SARS patients reveals that monocyte/macrophages, not T cells, are the primary immune cell involved in SARS. Monocyte/macrophages are a more ancient defense against invading viruses, and represent the body's "innate immunity."
The picture of what happens in SARS now appears to be as follows: the virus infects macrophages which line the gas-exchange unit of the lung, called the alveolus. The macrophage responds by becoming activated, which involves synthesis of angiotensin I converting enzyme (ACE) and production of angiotensin II. Angiotensin II generated by the activated macrophage stimulates not only the macrophage itself, but neighboring macrophages. Activated macrophages promptly begin synthesizing and secreting additional cytokines, including tumor necrosis factor-alpha (TNF-alpha). TNF-alpha alone has been shown to cause the high fever, muscle aches, and malaise which all SARS patients experience. TNF-alpha also causes apoptosis of lymphocytes in the bone marrow, which could explain the low lymphocyte counts seen in SARS.
A few days later, the epithelial cells of the lung become damaged by the SARS coronavirus. They undergo cell death, in a process also accelerated by angiotensin II. Their ingestion by neighboring lung macrophages further activates the macrophages, increasing the synthesis of cytokines. More monocytes are recruited from the bloodstream, and take up residence in the lung, explaining the monocytic infiltrate in lung biopsy specimens.
The net effect is a clinical picture that resembles acute respiratory distress syndrome (ARDS). In this syndrome, death of epithelial cells results in progressive respiratory failure. Lung epithelial cells, once they are killed by smoke inhalation, chemotherapy such as bleomycin, radiation, or microbes, begin an often irreversible process of lung failure.
Evidence for this hypothesis is the extremely low mortality (4%) seen at Prince of Wales Hospital in Hong Kong, compared to the 20% mortalities seen at another hospital in Hong Kong and in Canada. The only difference was that the Prince of Wales hospital was aggressive in its use of steroids. It may be that steroids have more clinical usefulness than antiviral therapy.
Steroids do not cure all patients with ARDS, nor did they prevent death completely at Prince of Wales hospital. GenoMed therefore suggests the use of a "sartan," at a dose low enough not to lower blood pressure, for all patients suspected of SARS. As prophylaxis, this approach should be of less risk than recommending the use of prophylactic steroids, since not all fevers are due to the SARS virus. Most pneumonia will still be due to other microbes, for which appropriate antibiotics exist, and whose course may be aggravated by steroids. The use of steroids should be reserved for patients with progressive SARS despite earlier therapy with a "sartan."
If the "sartan for SARS" hypothesis is confirmed, then an obvious additional hypothesis to test will be "ARBs for ARDS."
About GenoMed
GenoMed, Inc. is a medical genomics company whose mission is to improve patient outcomes by identifying the molecular pathways that cause disease. A St. Louis Business Journal article (http://www.stlouis.bizjournals.com/stlouis/stories/2002/05/13/story8.html ) first reported that the company has applied for patents based on its finding that the ACE gene is associated with a large number of common diseases. The Company has filed worldwide patent applications on its new treatments, and is eager to license them globally. GenoMed's research results are more fully described on its website, www.genomedics.com
For questions, please contact GenoMed at 314-977-0110, FAX 314-977-0042, email: dwmoskowitz@genomedics.com or dpollack@genomedics.com , or visit GenoMed at www.genomedics.com.
SOURCE GenoMed, Inc.
CONTACT: Dave Moskowitz, dwmoskowitz@genomedics.com, or David Pollack,
dpollack@genomedics.com, both of GenoMed, +1-314-977-0110, or fax,
+1-314-977-0042/
Web site: genomedics.com |
