Biopharming the future? – A powerful new approach

Biopharming offers a new and powerful approach when it comes to tackling Ebola and other diseases

The has been a resurgence of interest into therapeutics to treat diseases, this was caused by the largest ever Ebola virus outbreak in Africa, with a handful of patients being treated with an experimental drug. The experimental drug called ZMapp, is a combination of three varieties of humanised monoclonal antibodies, which in turn bind, in vivo, to proteins on the surface of the Ebola virus. This represents an exquisite tour de force of genetic engineering.

The ZMapp drug is created from genetically engineered tobacco plants, which have been infected with genetically engineered plant viruses. The infection is monitored in the tobacco plants over a week, with the virus (which is completely harmless to humans and animals) producing huge amounts of antibodies. The plants are then harvested and homogenized and the antibodies are purified and formulated for administration. The antibodies then bind to proteins of the Ebola virus, the infected patients body reacts with a humoral (antibody) and cellular (lymphocyte) response to the virus.

A report published in the journal Nature last week reported a study of ZMapp in monkeys who have been experimentally infected with the EBola virus.All 18 of the rhesus macaques treated with the experimental drug ZMapp recovered. Even the macaques which were not administered with the treatment until five days after the infection survived as well. Nature’s press release stated;

Three doses of ZMapp, administered at three-day intervals starting on day three, four or five after rhesus macaques were infected with Ebola virus, resulted in the survival of all 18 animals,” while “the three rhesus macaques that did not receive ZMapp all succumbed to Ebola virus infection by day eight.”  The drug “reversed severe Ebola virus disease symptoms such as excessive bleeding, rashes and elevated liver enzymes.

The findings have been very encouraging especially as they provide precisely the evidence of efficacy needed for regulatory approval of ZMapp, which will be evaluated under the “animal rule” by the FDA. This rule applies to the development of dugs when human efficacy studies are not feasible or ethical.

Creating medicine from plans is not a new phenomenon. Many common medicines, such as; morphine, codeine, cocaine and laxatives like Metamucil are all purified from plants. Biopharming is a very new approach and lies in using genetically engineered techniques to induce crops such as corn, tomatoes and tobacco to produce high concentrations of high value pharmaceuticals.

Around 15 years ago biopharming emerged with great promise, with clinical trials of vaccines and drugs which had been created in bananas, tomatoes and tobacco. Although the field confronted the zeal and risk aversion of regulators. Fast forward to 2002, a company called Ventria purified two human proteins from genetically engineered rice and that when added to oral rehydration solution that had been given to children with diarrhoea, it shortened the duration the symptoms and reduced the chance of recurrence.  The potential revolution of public health was blocked by the FDA. In 2010 Ventria approached the FDA again for recognition that the two proteins which are found in human tears and breast milk, are recognised as safe however they received no response. With no FDA endorsement Ventria were unwilling to market their product and with this depriving children in developing countries of a life saving therapy.

USDA’s rules on the cultivation of the biopharmed plants in the field impose highly prescriptive, one-size-fits-all “design standards,” as contrasted with “performance standards,” which would specify an end point such as gene-transfer below a certain level–that must be achieved by whatever means.  USDA’s regulation fails to take into account the actual risks of a given situation.

The risk of drugs which are made from plants getting into food products is now virtually non existent. This is due to companies involved in the production of these drugs have facilities with rigidly controlled environments and mainly use tobacco. This type of approach received huge backing in 2010 with more than $80 million being invested into facilities by the federal Defence Advanced Research Projects Agency. This was invested to expand the tobacco growing capacity at several companies.

The investment was driven by DARPA’s desire to expand the nation’s ability to respond with new drugs and vaccines to emerging diseases or attacks with biological agents.  These sorts of facilities, which have a high degree of control over growth conditions, are essential for the reproducible production of high quality drugs.  This constructive public-private collaboration set the stage for ZMapp, the Ebola drug, to be produced by one of the companies Kentucky Bioprocessing.

When there is urgency in producing a new drug or vaccine, the biopharming approach used for ZMapp has palpable advantages, and it is also being constantly improved.  Over the past several years, for example, as the engineering of the viral vectors has been refined, so has “host plant engineering,” the crafting of genetic changes that make foreign proteins that are synthesized in the plants more “human like” and less “plant like.”  (The changes have come around in the enzymes that put sugar residues on proteins after they are synthesized.)  This makes the antibodies more efficient in eliciting a robust immune response when they are administered to patients.

Another advantage of biopharming generally is that is offers great potential for cost cutting: The energy for product synthesis comes from light (sun or artificial), and the primary raw materials are water and carbon dioxide.

As well as this bipharming offers tremendous flexibility and economy when adjustments in production are needed. Doubling the amount of crop needed costs far less than doubling the size of a building in terms of paying for bricks and mortar. This then allows drug companies to invest in facilities until later on in the clinical testing cycle or until the market for the new drug can be estimated accurately.

For Ebola and many other diseases, if we are to reap what biopharming sows, we will need continued public/private collaboration which will include not only more funding but also reasonableness from regulators, tolerance from the food industry and a shred of decency from the anti-genetic engineering lobby.

Alex Carson

PiR Resourcing leaders in senior life science resourcing. For more news and information, you can follow us on Twitter and LinkedInFor all our latest roles in the Life Science sector please click here

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