Tomatoes and Parkinson's Disease: Can This Humble Fruit Pave the Way for Better Parkinson’s Treatment Options?

From memory to motivation to motor control, the neurotransmitter dopamine is involved in several key aspects of Parkinson’s disease (PD) development. This neurotransmitter is created from L-dopa, the current gold standard of PD treatment. 

But L-dopa isn’t without its costs, both literally and figuratively. It’s not cheap to produce and can come with some serious side effects. As over 10 million people worldwide are currently living with PD, researchers are looking to find a better and more accessible way to treat with L-dopa — and they might have achieved this using the humble tomato fruit.

What’s the Link Between Dopamine and Parkinson’s Disease?

Although the four cardinal symptoms of PD are movement-related — tremors, rigidity, bradykinesia or slow movement, and balance instability — the disease can also cause dementia or confusion, apathy, fatigue, anxiety, and depression. 

Dopamine — or rather, the lack thereof — is at the root of all of these symptoms. The development and progression of PD stems from the deterioration of dopaminergic neurons, which are collections of cells in a brain region called the substantia nigra. The neurons in this critical brain region make dopamine to control motor function and rapidly degenerate in PD patients. As PD progresses, more and more dopaminergic neurons become dysfunctional, worsening symptoms and making the detrimental side effects of synthetic L-dopa more pronounced. 

Also known as levodopa, L-dopa is a revolutionary therapy for millions of people living with PD; however, the medication also has some downsides. Synthetic L-dopa can cause undesirable side effects, including nausea, vomiting, and dizziness. Up to two-thirds of L-dopa users develop mild to severe dyskinesias, which are involuntary, erratic, and jerking movements. In addition to these side effects, the accessibility and affordability of L-dopa drugs are limited for many people, as the medication’s average cost is $2,500 per year. 

Due to the adverse side effects that synthetic L-dopa can cause, the solution may lie in L-dopa medications from a natural source. 

Engineering Tomatoes to Contain L-Dopa

Researchers out of the John Innes Centre in the UK hypothesized that tomatoes were the perfect fruit to be genetically modified into a natural source of L-dopa. Published in Metabolic Engineering in November 2020, the results from this study indicate that genetically modified tomatoes are a low-cost and accessible alternative to synthetic L-dopa medications. 

Although some plants produce L-dopa, like the beetroot, they don’t contain it in their flesh for us to consume. Instead, the L-dopa is used entirely to create betalains, compounds that give certain vegetables their red and yellow coloring. The legume Mucuna pruriens, also known as the velvet bean, contains high amounts of natural L-dopa in its seeds and has been used to manage PD symptoms. However, the harvesting and processing of the bean is a complicated process.

So, the UK research group chose tomatoes because they don’t produce betalain — meaning, the plant wouldn’t use up all of its L-dopa to make betalain — and the fruit is easily and widely cultivated.

The researchers began the process by modifying tomatoes to carry the gene CYP76AD6, which is found in beetroot and encodes for the enzyme responsible for synthesizing L-dopa. This enzyme, tyrosinase, uses the amino acid tyrosine to create L-dopa in plants. Therefore, the overexpression of this gene led to the tomatoes creating L-dopa naturally from tyrosine. Rather than use tyrosine-rich plants — which tend to be betalain-producers — the research team used the naturally lower-tyrosine tomato and engineered it to become abundant in the amino acid.

In a second experiment, the research team did just that. L-dopa-rich tomatoes were crossbred with tomatoes carrying the gene MYB12. This gene is considered a metabolic master regulator in tomatoes, generating elevated levels of tyrosine. These crossbred tomatoes boasted a 30% increased L-dopa content compared to the tomatoes with just the CYP76AD6 gene. 

The flesh of the hybrid tomatoes contained 150 mg of L-dopa per kilogram. As a standard Levodopa dose is 300-500 mg per day, this could be achieved with approximately 2 kilograms of fresh tomatoes.  

Does a Tomato a Day Keep Parkinson’s Disease at Bay?

So, is this research suggesting that PD patients should be stuffing themselves with genetically modified tomatoes to get their L-dopa dose? Not necessarily, as it would equate to over 16 tomatoes per day. Rather, the researchers aim to create a sustainable and scalable model of extracting L-dopa from the tomatoes and developing a purified L-dopa pharmaceutical. With the goal to provide treatment to areas with limited resources or access to synthetic L-dopa, these modified tomatoes could be easily grown, scaled to a larger production, and processed locally. 

Clinically speaking, natural sources of L-dopa tend to produce better therapeutic outcomes with fewer side effects than synthetic L-dopa. However, as L-dopa medications from these genetically modified tomatoes have not been studied in humans with PD, we don’t yet know the full implications and long-term outlook of the treatment. 

Key Takeaway From This Research:

• Genetically modified tomatoes with overexpression of the genes CYP76AD6 and MYB12 leads to the natural production of L-dopa, the precursor to dopamine.
• Synthetic L-dopa drugs are considered the gold standard for Parkinson’s disease treatment. However, these medications come at a cost — both literally, to the tune of $2,500 per year, and figuratively, in that they can cause debilitating side effects.
• These genetically modified tomatoes may be a low-cost, accessible, and scalable option for producing natural L-dopa medications to treat Parkinson’s disease locally and worldwide.

References:

Abbott A. Levodopa: the story so far. Nature. 2010;466(7310):S6-S7. doi:10.1038/466S6a

Breitel D, Brett P, Alseekh S, Fernie AR, Butelli E, Martin C. Metabolic engineering of tomato fruit enriched in L-DOPA [published online ahead of print, 2020 Nov 23]. Metab Eng. 2020;S1096-7176(20)30181-6. doi:10.1016/j.ymben.2020.11.011

Cacabelos R. Parkinson's Disease: From Pathogenesis to Pharmacogenomics. Int J Mol Sci. 2017;18(3):551. Published 2017 Mar 4. doi:10.3390/ijms18030551

Ovallath S, Sulthana B. Levodopa: History and Therapeutic Applications. Ann Indian Acad Neurol. 2017;20(3):185-189. doi:10.4103/aian.AIAN_241_17

Understanding Parkinson's Statistics. https://www.parkinson.org/Understanding-Parkinsons/Statistics. Published 2020. Accessed December 10, 2020.