Reports of Ebola had appeared to recede in the last few weeks; however the news of Dr. Martin Salia's death in the US on Monday was a reminder that the fatal disease is very much still a threat to the entire world. President Barack Obama met with Congress on Tuesday to request $6.18 billion in order to fund research to fight the Ebola virus. In total there have been 10 patients treated for Ebola in the US to date, with 2 ending in death. This shows that when caught early and given the correct treatment, there is a good chance of recovery but increased funding is still crucial in order to contain the disease nationally and internationally.
There are several Ebola research efforts ongoing in the San Diego area which will benefit from the increased funding if it is granted by Congress. The main four companies or institutes contributing in the race to provide an Ebola treatment are Mapp Biopharmaceutical, The Scripps Research Institute, Aethlon Medical and Leading Biosciences.
Leaf Pharmaceutical, a San Diego based arm of Mapp Bio is responsible for the development of the antiretroviral drug called ZMapp. The drug contains three humanized monoclonal antibodies which are sourced from the plant Nicotiana. Monoclonal antibodies are created in the laboratory and are designed to attach to specific cells and mimic natural antibodies produced by the body during an immune response.
The drug has been used during this year's Ebola outbreak however no clinical trials in humans have taken place thus far to test its safety or efficiency. It was reported that Martin Salia received the experimental drug ZMapp late into his treatment at Nebraska Medical Center along with blood plasma from a surviving Ebola victim. Unfortunately both were unsuccessful as Dr. Salia was in a very critical condition and eventually went into cardiac arrest. The drug has been used for 7 Ebola patients thus far, with 4 recovering successfully, prompting for the acceleration of the drug's production. Mapp Bio is currently preparing for Phase I clinical trials aiming to initiate in January.
How Does ZMapp Work?
As very little information is currently known about the antiretroviral drug ZMapp, The Scripps Research Institute has been helping through research on its structural basis which will help gain knowledge on its function. Scientists at the Scripps Research Institute have very recently identified weak spots on the surface of the Ebola virus which the ZMapp drug targets. A 3-D structure is to be released in the journal Proceedings of the National Academy of Sciencesthis week which displays how the ZMapp antibodies interact with and work on the Ebola virus (See Figure 1).
Figure 1: 3D image produced by an electron microscope showing how the three monoclonal antibodies (red, blue and yellow molecules) in ZMapp interact with the Ebola virus (grey molecule).
Using electron microscopy, it can be seen that ZMapp works by two of the antibodies binding near the base of the virus, preventing its entry into cells. One antibody then binds at the top of the virus which scientists suggest may act as a beacon, attracting attention for the immune system to identify the site of infection. Research released in August reported that the Ebola virus has undergone over 300 genetic changes however luckily the sites that the antibodies attach to remained unchanged.
Another San Diego company, Aethlon Medical, is also contributing to research efforts and has produced a medical device called the Hemopurifier which aims to remove virus particles from the blood via dialysis. More information on the Hemopurifier and how it was recently used on an Ebola patient can be found in our past blog post.
Leading Bioscience plan on submitting an application with the U.S. Food and Drug Administration to test its treatment called LB1148 in helping Ebola victims with multi-organ failure linked to hypovolemic, hemorrhagic or septic shock. In the meantime, Leading Bioscience will offer LB1148 to clinicians upon request, otherwise known as compassionate use.