Curing Ebola with Mice and Tobacco?

The two American healthcare workers who contracted Ebola virus in West Africa and were transported back to the US seem to be showing signs of improvement after being given an experimental medication. Dr. Kent Brantly and Nancy Writebol arrived at Emory University Hospital in Atlanta earlier this week. Both had been flown to the US by a specially equipped hazmat air ambulance.

An experimental drug called ZMapp had been flown to Liberia to treat one of the Americans, and Dr. Brantley had requested that Mrs. Writebol receive the medication. The medication has to be stored at subzero temperatures, and must then be slowly rewarmed to room temperature before administrating it, a process estimated to take 8-10 hours.

During that time, Dr. Brantly’s health deteriorated dramatically and it was decided to give him the ZMapp instead. Within an hour, Brantly’s condition improved- his breathing was no longer labored and a rash he had was gone. When he arrived at Emory Hospital, he actually walked from the ambulance into the hospital. He remains in a specially designed isolation room.

Mrs. Writebol also received ZMapp, although it seemed she needed a second dose to show enough improvement to allow her transport to the US.

What is ZMapp?

ZMapp is an experimental drug produced by  a collaboration  between  Mapp  Biopharmaceutical,  Inc., LeafBio   (San  Diego,  CA),  Defyrus  Inc.  (Toronto,  Canada),  the  U.S.  government  and  the  Public  Health  Agency  of  Canada (PHAC).  It is a “cocktail” of 3 antibodies which work against Ebola virus. Although it had been tried on rhesus monkeys, it had not yet been used in humans.

Y-shapped-antibodyAn antibody is a protein produced by the body’s immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Each type of antibody is unique and defends the body against one specific type of antigen.

To produce ZMapp, researchers injected mice with a protein that is specific to Ebola. Three antibodies produced by the mice that stuck to different part of the Ebola protein were isolated. These antibodies couldn’t be injected into humans because they would be recognized as “foreign” and would cause an immune response to the treatment.

So the researchers had to clone the genes that produced the antibodies and then carefully swap out parts that are specific to mice with human counterparts- all without altering the important parts that recognize the ebola protein.

In order to produce large enough quantities of the new “humanized” antibodies they then inserted the gene into cells from a tobacco plant.  These cells can act like little factories, and can produce large amounts of the antibody without all the “overhead” required by using animal systems.

ZMapp had been tested in rhesus macaques, with promising results and was working toward be able to begin trials in humans. Even though the drug has not been approved by the FDA, drugs can sometimes be given under the concept of “compassionate use.” “Compassionate use” is the use of an investigational drug outside of a clinical trial to treat a patient with a serious or immediately life-threatening disease or condition who has no comparable or satisfactory alternative treatment options.

The use of ZMapp for Dr. Brantly and Nancy Writebol has stirred up some controversy. With so many dying as a result of Ebola in West Africa, why were only two Americans given the drug? What is to be done for those in Africa still suffering from the disease?

This is certainly a valid point. In general the World Health Organization (WHO) has erred on the side of caution in using experimental drugs in outbreak situations. WHO spokesman Gregory Hartl cautioned that health authorities “cannot start using untested drugs in the middle of an outbreak, for various reasons.”

But now, WHO has decided to convene a panel of medical ethicists next week to consider whether experimental drugs should be more widely released. Dr Marie-Paule Kieny, Assistant Director-General at the World Health Organization said:

“We are in an unusual situation in this outbreak. We have a disease with a high fatality rate without any proven treatment or vaccine. We need to ask the medical ethicists to give us guidance on what the responsible thing to do is.”

What do you think should be done?

 

 

Michele R. Berman, M.D. was Clinical Director of The Pediatric Center, a private practice on Capitol Hill in Washington, D.C. from 1988-2000, and was named Outstanding Washington Physician by Washingtonian Magazine in 1999. She was a medical internet pioneer having established one of the first medical practice websites in 1997. Dr. Berman also authored a monthly column for Washington Parent Magazine.

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