Oklahoma City, OK – Researchers at the Oklahoma Medical Research Foundation (OMRF) have successfully designed a highly potent inhibitor for Memapsin 2, the enzyme believed to be directly responsible for Alzheimer’s disease.
The same team of scientists at OMRF, led by Jordan Tang, Ph.D., identified and produced Memapsin 2 earlier this year. This study was published in the Proceedings of the National Academy of Sciences on February 15, 2000. On April 12, 2000, a paper outlining the design and construction of the inhibitor to stop Memapsin 2 will be published in the Journal of the American Chemical Society. Researchers at OMRF include: Tang, Jacques Ermolieff, Xinli Lin, Gerald, Koelsch, Debbie Downs and Dongwoo Shin. Arun K. Ghosh of the University of Illinois at Chicago also collaborated on the project.
OMRF President J. Donald Capra, M.D. noted that “..it is important to realize that while we are still in the early stages of understanding how to stop Alzheimer’s disease, the discovery of the Memapsin 2 enzyme and the subsequent design of its inhibitor are critically important.”
Memapsin 2, also known as “beta-secretase,” is one of two protein-cutting enzymes, called proteases, whose over-activity is believed to lead to Alzheimer’s disease. Memapsin 2 works with another enzyme (called “gamma-secretase”) to cut a longer protein called Amyloid Precursor Protein (APP). The by-product from the cut is known as beta-amyloid, or “A-beta.” A-beta then accumulates in the brain and causes “plaques and tangles” which are evident in Alzheimer’s patients. On March 22, the Journal of the American Medical Association published a study on the correlation between elevated levels of A-beta and Alzheimer’s disease.
The next step for the OMRF team was to create an inhibitor for Memapsin 2. Dr. Jordan Tang is world renowned for his work concerning this family of proteases, and such knowledge led to the design of a highly potent inhibitor for Memapsin 2. The enzyme and inhibitor concept for Memapsin 2 is similar to the “protease inhibitors” which have been created to fight HIV and AIDS. Tang’s research efforts on the basic principles of this type of enzyme/inhibitor contributed to the speedy design of the Memapsin 2 inhibitor.
“No other lab has achieved this level of design and potency of a Memapsin 2 inhibitor,” said Dr. Tang. “We are hopeful that the design of the Memapsin 2 inhibitor will eventually lead to a drug which will effectively treat Alzheimer’s disease.”
Because Memapsin 2 only cuts the larger protein in a very specific place, Tang and his team were able to create a “decoy”: its chemical structure resembled the area where Memapsin 2 always cuts, but instead of cleaving the protein, the inhibitor disables the enzyme. Memapsin 2 is attracted to the decoy; it “thinks” it is cutting the larger protein.
The inhibitor acts as a sticky substance, similar to a “chemical chewing gum.” Once Memapsin 2 adheres to the decoy, the enzyme is completely disabled. Thus, the enzyme causing Alzheimer’s disease is stopped before it can cut the protein, create A-beta, and make the plaques and tangles associated with the disease.
Tang added: “the discovery of the Memapsin 2 inhibitor is a significant step towards designing a drug that would stop Alzheimer’s disease. For the general public, the discovery of the inhibitor is a step forward in the right direction towards the eventual creation of a drug.”
It is critical to note while this progress is an important step towards a successful treatment of Alzheimer’s disease, the present Memapsin 2 inhibitor should not be mistaken as a drug itself. The Oklahoma Medical Research Foundation does not have a drug for the treatment of Alzheimer’s disease at this stage of research. Negotiations are currently underway with a number of major pharmaceutical companies to achieve this goal.
Chartered in 1946, OMRF is a private, non-profit, biomedical research institution which employs over 400 scientists, physicians, technicians, and administrative and support personnel. Along with Alzheimer’s disease, OMRF focuses on several critical areas of research: cancer, heart disease, diabetes, lupus and other autioimmune diseases, stroke, AIDS, aging, children’s diseases and genetic disorders.
For additional information, including past press releases, news articles, or graphics, please contact Andrea Miles at 405-271-7159. The information can also be obtained from OMRF’s web site: http://www.omrf.ouhsc.edu/
Stopping the Alzheimer’s Chain Reaction
OMRF Researchers Develop Inhibitor for Alzheimer’s Disease Enzyme
(Oklahoma Health Center News, May 2000)
Nickles Applauds Oklahoma Medical Research Foundation
Photos from April 12 Press Conference
Researchers Find Inhibitor for Alzheimer’s Enzyme
(Blackwell Journal-Tribune – Associated Press, April 30, 2000)
Oklahoma Researchers Develop Inhibitor for Enzyme Responsible for Alzheimer’s Enzyme
(Alva Review-Courier, April 24, 2000)
Breakthrough! Alzheimer’s Work Typifies Needs of Research
(The Sunday Oklahoman, April 16, 2000)
Exciting Finding – State Researchers on Cutting Edge
(Tulsa World, April 16, 2000)
Alzheimer’s Breakthrough Discovered in OKC
(Oklahoma City Friday, April 14, 2000)
OU Researchers Close in on Potent Alzheimer’s Weapon
(Tulsa Business Journal, April 14, 2000)
OMRF Finds Alzheimer’s Inhibitor
(The Journal Record, April 13, 2000)
Researchers Identify Alzheimer’s Enzyme Inhibitor
(The Los Angeles Times, April 13, 2000)
Oklahoma Researchers Find Inhibitor for Alzheimer’s
(Holdenville Daily News – Associated Press, April 13, 2000)
Researchers Offer Hope for Alzheimer’s
(Claremore Progress – Associated Press, April 12, 2000)
State Researchers Step Closer to Alzheimer’s Drug
(The Daily Oklahoman, April 12, 2000)
Oklahoma Doctors Identify Possible Alzheimer’s Inhibitor
(Hugo Daily News – Associated Press, April 12, 2000)
Oklahoma Researchers Find Inhibitor for Alzheimer’s Enzyme
(The Norman Transcript – Associated Press, April 12, 2000)
Researchers Find Inhibitor for Alzheimer’s Enzyme
(Oklahoma Daily – Associated Press, April 12, 2000)
Oklahoma Researchers Design Inhibitor for Alzheimer’s Enzyme
(Pauls Valley Daily Democrat – Associated Press, April 12, 2000)
State Researchers Design Inhibitor for Alzheimer’s
(Shawnee News-Star – Associated Press, April 12, 2000)
Remedy a Step Closer
(Tulsa World, April 12, 2000)
Researchers Find Alzheimer’s Inhibitor
(Woodward News – Associated Press, April 12, 2000)
Newsline 9 Health Watch Team Breaks Story of Medical Breakthrough
(Hinton Record, March 8, 2000)
Previous Alzheimer’s Discovery – February 15, 2000
Background: OMRF’s Breakthrough Discovery on Alzheimer’s Disease
