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Thursday, August 7, 2014

An update on the Ebola virus disease "cure"

I wanted to update my previous post on the Ebola virus disease (EVD) cure. More information has come to light and some of the descriptions that I previously posted were not accurate.

An experimental drug (ZMapp) consisting of three monoclonal antibodies against Ebola virus (EV) proteins was given to two Americans infected with EV. After the injection, the conditions of both subjects improved, and they have subsequently flown back to the U.S.

First a technical detail. It turns out that the ZMapp monoclonal antibodies are made in a non-traditional fashion in tobacco plants. These plants are transformed with the antibody genes (genetically-modified organism) which are expressed in the tobacco leaves which can be harvested for the monoclonal antibody. Typically monoclonals are synthesized from hybridomas made by fusing antibody-producing cells with myeloma cells. These hybridomas can be grown in large culture vessels.

From a New York Times article on ZMapp:
"Monoclonal antibodies produced by pharmaceutical companies for use in treating cancer or other diseases are typically made in genetically engineered cells of mammals grown in vats. But Mapp chose to use plants instead because large quantities can potentially be produced more quickly and cheaply."
Second, the ZMapp drug contains antibodies developed by the company Mapp (which has been in the news) and antibodies developed by a second company Dreyfus:
"It turns out another tiny company, Defyrus, based in Toronto, was independently developing a similar treatment with the Public Health Agency of Canada. The companies agreed to combine the best of their antibodies into a single cocktail called ZMapp, which is what the two American aid workers received. The data for ZMapp in monkeys has not been published but is said to be substantially better than for the predecessor drugs."
Third, I wanted to comment on the report by Dr. Sanjay Gupta which gave rise to the somewhat exaggerated claims of a"miracle cure" :
"Brantly asked that Writebol be given the first dose because he was younger and he thought he had a better chance of fighting it, and she agreed. However, as the first vial was still thawing, Brantly's condition took a sudden turn for the worse.

Brantly began to deteriorate and developed labored breathing. He told his doctors he thought he was dying, according to a source with firsthand knowledge of the situation.

Knowing his dose was still frozen, Brantly asked if he could have Writebol's now-thawed medication. It was brought to his room and administered through an IV. Within an hour of receiving the medication, Brantly's condition dramatically improved. He began breathing easier; the rash over his trunk faded away. One of his doctors described the events as "miraculous."

By the next morning, Brantly was able to take a shower on his own before getting on a specially designed Gulfstream air ambulance jet to be evacuated to the United States.

Writebol also received a vial of the medication. Her response was not as remarkable, according to sources familiar with the treatment. However, doctors on Sunday administered Writebol a second dose of the medication, which resulted in significant improvement.

She was stable enough to be evacuated back to the United States."
The above passage sounds like the script to a movie, which perhaps is what Dr. Gupta had in mind. It is unclear how sick Brantly and Writebol were and where they were in the disease progression when they received the injection of ZMapp. For example, it is possible that Brantly was already improving, and the drug accelerated his recovery. Most importantly, how much was the improvement a placebo effect?

It is important to collect data on the efficacy of ZMapp from more than two patients in a more scientific and controlled fashion. That being said, there is cautious optimism among experts that ZMapp has helped the two American patients, and hopefully they both go on to a full recovery. In the meantime the tobacco plants (Figure 1) need to be working overtime making ZMapp to be given to more patients.
Figure 1. The anti-Ebola Virus drug ZMapp is made in the leaves of tobacco plants like these (from The New York Times).

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