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Parkinson's disease drug Carbidopa has significant anticancer effects in experimental models of disease


A research has shown the Parkinson's disease drug Carbidopa displays significant anticancer effects in both human cell lines and mice when given at normal patient dosage levels.

This discovery, which is published in the Biochemical Journal, may explain the low incidence of many cancers ( with the exception of melanoma ) in patients with Parkinson's disease and could lead the way to Carbidopa being repurposed as an anticancer medication.

Parkinson's disease is a degenerative neurological disorder that mostly influences a person's movement and motor skills, with symptoms including shaking, rigidity and difficulty in walking.
These effects are a result of lower than normal production of dopamine, a chemical that sends behavioural signals from the brain to the body.
While there is currently no cure for the condition, there are a number of treatments that act to reduce the severity of the symptoms of Parkinson's disease.
Dopamine itself cannot be used as a drug, as it will not cross the blood-brain barrier. However, one of the chemicals that forms dopamine, Levodopa ( L-DOPA ) can cross into the brain and is converted into dopamine once there.

Levodopa has been used to treat Parkinson's disease symptoms for many years, but when used alone can result in side effects such as nausea. This is because only 5-10% of Levodopa taken as a drug crosses the blood-brain barrier, with the rest being converted into dopamine elsewhere in the body.
The drug Carbidopa does not cross into the brain, but when taken with Levodopa prevents its conversion into dopamine outside the brain and reduces side effects for patients.

Many studies have shown that patients with Parkinson's disease have a lower rate of most cancers compared with the general population.
As most patients in these studies were treated with a combination of Levodopa and Carbidopa, it is possible that one or both of these drugs could exhibit anti-cancer properties and contribute to the lower incidence of cancer observed in these patients.

Earlier studies showed that Levodopa does not have anticancer properties, but until now the potential anticancer properties of Carbidopa have not been investigated.

Carbidopa is never used by itself as a drug for any disease. Researchers believe that the reduced incidence of most cancers in Parkinson's disease patients is due to Carbidopa.
Researchers have also postulated that the increased incidence of melanoma in Parkinson's disease patients is most likely due to Levodopa, and not due to Carbidopa, because Levodopa is the precursor for melanin synthesis, a metabolic pathway that occurs exclusively in melanocytes.

In the current study, researchers tested the effects of Carbidopa on a human pancreatic cancer cell line and also in mouse models of pancreatic cancer.
They found that Carbidopa significantly inhibited cancer cell growth both in the cell line and in the mice.

The researchers believe that Carbidopa is likely to have wide ranging anticancer effects, but chose to focus on pancreatic cancer for this study because of the low survival rate and limited treatment options for this form of the disease.
Pancreatic cancer, especially the pancreatic ductal adenocarcinoma, is the most lethal of all cancers with a dismal survival rate.

The recommended dose of Carbidopa for Parkinson's disease patients is 200 mg/day, but when given at a dose even as high as 450 mg/day, there are no side effects.
While this study was not carried out in humans, the dose of Carbidopa given to the mice that stopped tumour growth was equivalent to a dose in humans of less than 400 mg/day, which is within the dose range considered to be safe for patients.

The aryl hydrocarbon receptor ( AhR ) protein plays a critical role in cancer and activation of this protein has shown promise for treating a variety of different cancers including breast, colon and pancreatic cancer.
Carbidopa activates AhR and believe this may explain, at least in part, its anticancer properties. ( Xagena )

Source: Biochemical Society, 2017

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