Carrots that break barriers

Last 1^st May the FDA approved the first recombinant protein produced in plant cell cultures to use it as a medicine.  It looks like the pharmaceutical market has been opened for the production of drugs with green roots. 

Gaucher’s disease is a genetic disorder that affects 1 in 50000 people, being more common (1 in 450 live births) among Ashkenazi Jews, those coming from  Central and Eastern Europe, where 1 in 10 people carry the problematic genetic versions.  Patients affected by Gaucher’s disease have inherited two defective copies (one from the father and one from the mother) of one of their genes, the one coding for the enzyme glucocerebrosidase, in charge of breaking lipids. Defects in this protein cause the accumulation of lipids, above all in macrophages, damaging liver, spleen, bones and bone marrow and causing symptoms like anemia, enlargement of spleen or liver, bone pain etc.

However, as Gaucher’s patients only have one damaged gene and therefore they only lack one protein, there is a simple therapeutic approach to help them: producing the human protein using biotechnology and take it periodically. Till now, the only drug in the market was the injectable Cerezyme® (from the company Genezyme). To produce it, the glucocerebrosidase gene had been cloned and introduced in hamster cells, that are then cultured on a large scale to generate big amounts of the recombinant protein. Afterwards the enzyme is purified and then modified to improve its entry into the macrophages. Since the approval of Cerezyme® in 1994, patients improved their quality of life, as the drug reverted many of the disease’s symptoms. However, in 2009 and 2011, the hamster cell cultures used to produce Cerezyme® got contaminated by viruses and the company had to halt production, seriously affecting Gaucher’s patients, who have to be under treatment for life.

Bioreactors from Protalix Biotherapeutix

Meanwhile, the company Protalix Biotherapeutics, headquartered in Israel, was designing a different strategy to solve the problem:  clone the gene of human glucocerebrosidase and introduce it into carrot cells that are then cultured in bioreactors based on disposable plastic bags, much more economic than those used to culture mammalian cells. The final product, Elelyso®, doesn’t need to be modified because, as it has been produced in plants, it already displays the necessary characteristics to be easily uptaken by macrophages, also diminishing this way the costs of the final product. The activity of Elelyso® is similar to the one of Cerezyme® but the price will be 25% cheaper. Besides, carrot cultures are not target of the viruses that attack mammalians and this will help to guarantee a continuous supply to patients.

Despite the advantages of producing recombinant proteins in plant cultures, regulatory organisms used to be conservative regarding the platforms used to produce the drugs, as some contradictory data had been published regarding the immune response triggered by some plant-made recombinant proteins. The approval of Elelyso® has broken the first barrier and maybe it will represent the necessary proof to facilitate the entry into the market of cheaper alternatives with green origins.

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