From David Moskowitz, M.D.: ACE as “master” disease gene

A major medical story has been brewing for the past decade or so, but so far hasn’t been reported in the regular media.

The discovery involves a very well known enzyme called angiotensin I-converting enzyme, or ACE for short. ACE inhibitors have been used to lower blood pressure since the late 1970s, and are among the safest drugs used in medicine. An even safer class of drugs was marketed about 10 years ago, called angiotensin II receptor blockers, or “ARBs.” ACEI’s and, especially, their cousins, ARBs are considerably safer than aspirin, and are carried in every drugstore on earth. There are many drugs in each class. Some of the better ACEI’s are generic by now; the first ARB goes generic in 4 years.

It turns out ACE is a “master” disease gene, whose overactivity is associated with 3/4 of common diseases among Caucasians, and about 40% in African Americans.²

Thus inhibiting ACE, which has been possible since 1978, should delay most common diseases, and may add 5-10 years of lifespan. Not to mention cutting healthcare costs by keeping people out of hospital longer.

As just one corrollary, ACE inhibitors and ARBs may be a general viral antidote, useful against avian influenza as well as the common cold. Language describing this general approach to viral diseases was included in the Project BioShield II Act of 2005.⁸

It is the best possible thing that could have happened for global public health.

ACE inhibitors, when used at a high enough dose, have been able to reverse 90% of kidney failure.¹ Case reports showing unexpectedly good results in sickle cell disease,⁷ COPD (emphysema¹), West Nile virus encephalitis,⁵ psoriasis,⁵ and stage IV pancreatic cancer⁵ have also been published.

The angiotensin I-converting enzyme, discovered in 1950, is so called because it converts angiotensin I, a 10 amino acid peptide, into angiotensin II, an 8 amino acid peptide, by clipping off the terminal two amino acids.

References follow. 

1: Moskowitz DW. From pharmacogenomics to improved patient outcomes: angiotensin I-converting enzyme as an example. Diabetes Technol Ther. 2002;4(4):519-32. PMID: 12396747. (For PDF file, click on paper #1 at:
http://www.genomed.com/index.cfm?action=investor&drill=publications )

2: Moskowitz DW. Is angiotensin I-converting enzyme a “master” disease gene? Diabetes Technol Ther. 2002;4(5):683-711. PMID: 12458570 (For PDF file, click on paper #2 at:
http://www.genomed.com/index.cfm?action=investor&drill=publications );

3: Moskowitz DW. Is “somatic” angiotensin I-converting enzyme a mechanosensor? Diabetes Technol Ther. 2002;4(6):841-58. PMID: 12685804 (For PDF file, click on paper #3 at:
http://www.genomed.com/index.cfm?action=investor&drill=publications )

4: Moskowitz DW. Pathophysiologic implications of angiotensin I-converting enzyme as a mechanosensor: diabetes. Diabetes Technol Ther. 2003;5(2):189-99. PMID: 12871609 (For PDF file, click on paper #4 at:
http://www.genomed.com/index.cfm?action=investor&drill=publications )

5: Moskowitz DW, Johnson FE. The central role of angiotensin I-converting enzyme in vertebrate pathophysiology. Curr Top Med Chem. 2004;4(13):1433-54. PMID: 15379656 (For PDF file, click on paper #6 at:
http://www.genomed.com/index.cfm?action=investor&drill=publications )

6: Moskowitz DW. Acute oxygen-sensing mechanisms. N Engl J Med. 2006 Mar 2;354(9):975-7. PMID: 16510756 

7: Williams RM, Moskowitz DW. The prevention of pain from sickle cell disease using trandolapril. J Natl Med Assoc 2007 Mar (in press) 

8: Section 2151 of the Project BioShield II Act of April 28, 2005
(http://www.govtrack.us/congress/billtext.xpd?bill=s109-975)

David W. Moskowitz, MD, MA(Oxon.), FACP
Chairman, CEO & Chief Medical Officer
GenoMed, Inc.
"Our business is public health(TM)"
9666 Olive Blvd., Suite 310
St. Louis, MO 63132
website: www.genomed.com