Parkinson’s disease is a long term neurodegenerative disorder of the central nervous system, which affects the patients motor function. Parkinson’s is most common in the elderly around the ages of 60-80 years old, and affects male more than women. The most obvious symptoms are tremor, rigidity, akinesia and posture. The cause of parkinson’s disease in elderly is largely idiopathic although it is believed to be based on both genetic and environmental factors. There is also an increased risk in people who have had prior head injuries, on the other hand there is a reduced risk in smokers and caffeine drinkers. The impaired motor function arises from the death of cells in the substantia nigra which is a mid part of the brain, this therefore results in not enough dopamine. Parkinson’s is the destruction of dopaminergic neurons in the substania nigra.
There is no cure for parkinson’s disease other than treatment that is directed at improving current symptoms. Initial treatment is with the anti-parkinson drug levodopa also known as l-dopa. It restores dopaminergic neurotransmission in the corpus striatum which enhances the synthesis of dopamine in the surviving neurons in the substantia nigra. In new patients the therapeutic response to this drug is consistent and they rarely complain about the drug wearing off. Although with time the number of neurons reduces, and fewer cells are capable to take up levodopa and therefore converting to dopamine for storage and release. Relief from levodopa is only symptomatic and only lasts whilst the drug is in the body. The drug can also be co-administered with carbidopa which enhances the effect of levodopa on the central nervous system; however dopamine itself does not cross the blood brain barrier but it’s precursor levodopa does. It is actively transported into the central nervous system and is then converted back to dopamine in the brain. Large doses of levodopa is required to be administered as much of the drug is decarboxylated to dopamine; resulting in side effects such as nausea, cardiac arrhythmias, hypotension and vomiting. Carbidopa is a dopa decarboxylase inhibitor which extenuates the metabolism of levodopa in the gastrointestinal tract, so that it increases the availability of levodopa to the central nervous system. The addition of carbidopa lowers the dose of levodopa which therefore results in levodopa decreasing rigidity, tremors and other parkinsonism symptoms. Levodopa co-administered with carbidopa is an effective and potent drug regimen, the regimen is effective in two thirds of patients who suffer with parkinson’s in the first few years, then they see a decline in response during the third to fifth year of treatment.As the disease advances and the neurons continue to be lost, these anti parkinson drugs become less effective. (Pharmacology,2012, p.101)
Other than drug treatment there has also been some speculation around gut based treatments that parkinson disease arises from the gut and somehow affects the brain leading to the disease itself. There have been studies to support this idea as will be discussed.
This first study states that parkinson’s disease patients have digestive problems up to 10 years before they start noticing symptoms such as tremors. They also found evidence that people with parkinson’s have different gut bacteria in comparison to patients who don’t suffer with parkinsons, suggesting that the gut does have an effect in parkinsonism diagnosis. This article talked about a new study in mice that has shown that alpha synuclein fibres which build up in the neuron, in parkinson’s patients tends to influence brain neurons and see a difference within a few weeks. Alpha synuclein is a protein which is a sufficient amount within the human brain. It is also present in the gut, in terms of the brain it is situated more towards the ends of the neurons, it is known for the release of the neurotransmitter dopamine which is crucial in parkinson’s disease. Alpha synuclein has a wavy like structure, however in parkinson’s this structure alters and the protein mis-folds creating a toxic clump. When these accumulate into large masses they are known as lewy bodies.
The researchers carried out this study by looking at genetically modified mice which had an over production of alpha synuclein fibres. These mice were either raised in either one of the cages, one being a normal and a non sterile cage and the other being a germ free and sterile cage. The results were as followed the mice that were raised in the germ free and sterile cage showed fewer motor deficiency and less alpha synuclein found in their brains, whereas in comparison with the mice in the non sterile cage, it was found that they had developed parkinson’s symptoms, however antibiotics were given to these mice which did reduce there symptoms but suggested that there was something in their gut microbiome which was enhancing the symptoms. They then injected gut bacteria from patients who had parkinson’s into the germ free mice, who had no symptomatic change before however now after insertion they started to deteriorate and symptoms started to arise; although the gut bacteria that was taken from healthy patients did not have the same effect. Suggesting parkinsons may be diagnosed by the patients own gut bacteria. There conclusion from this study was, that they believe gut bacteria may be responsible for chemicals which are causing the brain to over activate certain parts, which therefore results in leading to alpha synuclein damage. The team now want to do further research and analyse gut bacteria in parkinsons’s disease patients and try to find out which microbes can be used as markers to diagnosis a patient, based off there gut bacteria, meaning they could screen a patient before parkinsonism symptoms arise and before the damage to the brain occurs.
Another review article also found evidence that, parkinson’s disease is based off a gut-brain theory and the changes in microbes in the gut are associated with the disease.The review article states that “up to 80% of parkinsons disease patients report gastrointestinal problems”. They believe that by cutting the connection between the brain and gut which happens to be the vagus nerve; halves the risk of even being diagnosed with parkinson’s. They also noticed the changes in the gut’s flora may be the starting point for the disease. The gut theory has been explained by a hypothesis which is Braak’s hypothesis in which he and some researchers used a systematic staging system to explain the progression of pakinson’s disease through the human brain. Stage one was were the lewy bodies were inserted in the back of the motor nucleus of the vagus nerve. They then spread through the brainstem, which resulted in motor symptoms occurring and parkinson’s disease would then be diagnosed. A follow up of 15,000 patients having done the surgery of severing the vagus nerve had also been discussed suggesting that, by severing the vagus nerve in half may halve the patient’s risk of being diagnosed with parkinson’s however; if the nerve is only severed partially patients were not then receiving the same benefit which was, that the vagus nerve between the stomach and brain may also be seen as an alternative pathway for parkinson’s disease to spread, by transferring alpha synuclein via the microtubule transport, which provides a mechanism of action which is the aftermath of the severing of the vagus nerve. The study also found that constipation was one of the most common symptom parkinson’s disease patients reported, they noticed that patients had been suffering from a long history of constipation before other symptoms arise and diagnosis as well. They believe that constipation and gut motility alter the gut’s microbial environment. Faecal transplants has also been recently used in clinics but, in non parkinson’s disease patients to strongly treat constipation.Although faecal transplants has been trialled in parkinson’s disease patients it has been seen to improve gut flora alongside, seeing changes in medication and diet which suggests it may slow the progression of the disease. Faecal transplant involves faeces of a healthy donor to be transplanted in a patient to restore a healthy balance of bacteria in the gut
There idea of gut based treatment was that, if the microbiome which is the microorganisms in a particular environment such as the gut, was altered in parkinson’s disease patients there may be potential to offer faecal transplants or a microbial pill treatment to alter the gut’s flora to either prevent or reverse the disease’s progression.It is possible that faecal screening may provide an early biomarker to test for neurological dysfunction and may slow down the progression in patients who are undiagnosed and at risk.
To conclude as stated above there has been evidence to support gut based treatments however there is still no cure for parkinsons disease. It is clearly evident that gut bacteria in parkinson’s patient does have an effect on being diagnosed.
Although in contrast there has also been surgery known as deep brain stimulation which places permanent micro electrodes in the brain which controls areas involved in movement this has been use to reduce loss of motor function symptoms in severe cases in which the drugs have been ineffective.