A genetically modified tomato enriched with the Parkinson’s disease drug L-DOPA has been produced by scientists at the UK-based John Innes Centre.
L-DOPA is used to treat Parkinson’s by compensating for dopamine, which is depleted in patients with the disease. The drug is made from tyrosine, an amino acid found in many foods. While it’s most commonly produced chemically, this version can cause unpleasant side effects.
Natural sources exist as well, but only a few plants contain measurable quantities, primarily in their seeds. These likewise can have negative effects on Parkinson’s patients due to other characteristics of the plant. The velvet bean, for example, is the most studied source, containing up to 10% L-DOPA in its seeds.
However, the bean itself causes elevated levels of tryptamines which can cause hallucinations. Using tomato plants as a natural source of L-DOPA could have the benefit of providing an alternative to those who experience adverse reactions, such as nausea or behavioral issues when taking the chemically synthesized version.
It may also have the impact of creating an affordable new source of this medication, particularly in developing nations where access to pharmaceutical drugs is limited.
A team at the research facility modified the fruit by introducing a gene found in beetroots responsible for the synthesis of L-DOPA. They inserted a gene encoding a tyrosinase, an enzyme that uses tyrosine to build molecules such as L-DOPA. This brought up the level of L-DOPA specifically in the fruit part of the plant and led to higher yields than those associated with L-DOPA production in the whole plant.
Tomatoes in particular were chosen to be modified with the drug as they are a widely cultivated crop and can be used for scaled-up production, potentially becoming a standardized natural source. The levels of L-Dopa achieved in the genetically modified tomatoes, 150mg per kg, were comparable to those observed in other L-DOPA accumulating plants without the drawbacks.
The goal from here is to create a production pipeline where L-DOPA is extracted from the tomatoes and purified into the pharmaceutical product.
“The idea is that you can grow tomatoes with relatively little infrastructure. As GMOs (genetically modified organisms) you could grow them in screen houses, controlled environments with very narrow meshes, so you would not have pollen escape through insects,” explained Professor Cathie Martin, a fellow of the Royal Forestry Society (RFS) and corresponding author of the study. “Then you could scale up at a relatively low cost. Local industry could prepare L-DOPA from tomatoes because it’s soluble and you can do extractions. Then you could make a purified product relatively low tech which could be dispensed locally.