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Diagnosis and treatment approach to Parkinson’s disease with special reference to microbiome and the gut

Dr. P. Rammanohar, MD (Ay)

Parkinson's disease (PD) is a neurodegenerative disorder that affects predominantly dopamine-producing (“dopaminergic”) neurons in a specific area of the brain called the substantia nigra. Symptoms generally develop slowly over the years. The classical features of Parkinson’s disease are a) Bradykinesia - slowness of movement, b) Tremor - Shaking of limbs, hand or fingers, c) Rigidity, d) Imparied posture and balance, e) Loss of automatic movements, f) Changes in speech, g) Difficulty in writing.

All these symptoms may not be seen in all the patients. A combination of slowness of movement, tremors and rigidity can make one to strongly suspect Parkinson’s Disease.

The current understanding of Parkinson’s disease has a primary focus on the changes that happen in the brain, specifically in the area called the substantia nigra that leads to a deficiency of dopamine in the body.

Unfortunately, effective treatment for Parkinson’s disease (PD) is not yet available. Treatment for each person with Parkinson’s Disease is customised considering his or her symptoms.

Treatments can include both medication and surgery. Lifestyle modifications are also recommended for the management of Parkinson’s Disease like getting more rest and exercise. Although there are many medications available for PD, none of them can bring about a cure, though these medications can manage the symptoms to a certain extent. Patients with PD take a variety of these medications — all at different doses and at different times of day — to manage symptoms.

The most commonly used medicine for Parkinson’s is Levodopa (also called L-dopa) is. L-Dopa is recognised as the best mediation at controlling the symptoms of PD, particularly slow movements and stiff, rigid body parts.

Levodopa works when brain cells convert it into dopamine, which is a chemical the brain uses to send signals that helps to move the body. People with Parkinson’s don’t have enough dopamine in their brains to control their movements.

Sinemet is a mix of levodopa and another drug called carbidopa. Carbidopa makes the levodopa work better so that its dose can be reduced to prevent side effects.

Safinamide (Xadago) is an add-on medicine that is prescribed when individuals taking levdopoa and carbidopa have a relapse of Parkinson’s symptoms that were previously under control.

There are other drugs called Dopamine agonists which simulate the action of dopamine. There are also other medicines that influence the activity of dopamine in the brain and can help in control of the symptoms of Parkinson’s Disease.

All these medications have the risk of side effects on long term use and can only mask symptoms. Studies have indicated that these medications cannot even prevent the progress of the disease.

The renowned neuroscientists of the world, Dr. V.S. Ramachandran recently recommended Ayurveda to treat Parkinson’s disease over. He has also expressed interest to collaborate with Indian doctors to study Ayurveda drugs as they have lesser side effects and could be more effective in treating Parkinson’s disease than allopathic drugs.

Dr. V.S.Ramachandran, is currently director, Centre for Brain and Cognition and distinguished professor with the neuroscience program and department of psychology, University of California, San Diego. He has been hailed as one of the most eminent neuroscientists in the world and was selected as one among the 100 most influential persons in the world in 2011 in a survey conducted by the Time magazine. He is very well known for his best selling books like Phantoms in the Brain and Tell-tale Brain.

In an interview during a visit to India, he explained that the Ayurveda drug Mucuna pruriensis (a variety of bean, rich in L-dopa and known in Sanskrit as Kapikacchu) was tested and proven in clinical trials to be more effective than allopathic drug placebo and synthetic L-dopa used to treat Parkinson’s disease, especially exhibiting fewer side effects.

Well, in this discussion, I do not intend to discuss about Mucuna pruriens, which as discussed above is being seriously considered as a safer and more effective alternative for the management of Parkinson’s even by modern scientists. The use of L-Dopa as well as Mucuna pruriens is based on the perception of Parkinson’s disease as a pathological process that is exclusively happening in the brain of the patients. The excessive presence of an abnormal protein called alpha–synuclein has been found in the brain regions of patients affected by Parkinson’s Disease.

Parkinson's disease is characterized by the buildup of a misfolded protein, called alpha-synuclein, in the cells of the brain. As more of these proteins begin to clump together, they cause nerve tissues to die off, leaving behind large swaths of dead brain matter known as Lewy bodies. As brain cells die, they impair a person's ability to move, think or regulate emotions.

And it is here that a completely new way of looking at Parkinson’s Disease emerges. The possibility that Parkinson’s Disease may actually have origins in the gut rather than the brain. And a number of studies in recent times have lend substance to this hypothesis. It all began with observations made in 2003 by German neuroanatomist Heiko Braak who demonstrated that people with Parkinson's disease also had accumulations of the misfolded alpha-synuclein protein in the parts of the central nervous system that control the gut. Hanseok Ko, Johns Hopkins, observed that the appearance of these neuron-damaging proteins is consistent with some early symptoms of Parkinson's disease, which include constipation. He went on to hypothesize that Parkinson's disease originates in the gut and then moves up to the brain.

Studies have pointed out to the possibility that the misfolded alpha-synuclein protein may travel from the gut to the brain through the vagus nerve. The vagus nerve runs like an electrical cable from the stomach and small intestine into the base of the brain. This possibility was experimentally proven when researchers injected guts of mice with misfolded alpha-synuclein in two groups, one with vagus nerve intact and the other with vagus nerve removed. They found that the misfolded alpha-synuclein traveled to the brain in the group of rats with intact vagus nerve.

A correlation has also been made between gut microbiota and Parkinson’s Disease. A number of studies have reported that individuals with Parkinson’s disease have a unique composition of gut microbes. Transplanting fecal microbes from patients into rodents predisposed to develop Parkinson’s can worsen motor symptoms of the disease and increase alpha-synuclein aggregation in the brain.

It is also suspected that inflammation in the gut triggered by microbes may have a role to play in the development of Parkinson’s Disease.

This is the most interesting part of our discussion. For centuries, Ayurveda has considered the gut, especially the lower intestine to be the primary seat of Vāta. The upward movement of Vāta known as Udāvarta is considered to be an underlying pathology in many diseases. It has been a fascinating experience to see clinical improvement in patients with Parkinson’s disease when treated with Ayurvedic medications and treatments that target the gut, especially to reestablish the natural functions of Apāna Vāta. In fact, this approach seems to give results more quickly in the clinical settings than the administration of Mucuna pruriens alone.

Three patients in different stages of the development of Parkinson’s Disease are followed up closely to see the improvements in clinical presentation with Ayurvedic treatment that focuses on correcting the functions of Vāta in the lower gut. In all three patients, constipation was found to be a cardinal symptom and the clinical improvement has been seen to be directly proportional to the improvement observed in constipation.

The Ayurvedic approach to the management of Parkinson’s Disease is clearly a bottom up approach starting from the gut and gradually moving towards the brain region, the head. Internal medications for Dipana and Pachana, followed by Snehapana and Virechana, the administration of Vasti and then treatments like Nasya and Sirovasti are found to bring remarkable clinical improvements in patients presenting in different stages of progression of Parkinson’s Disease.

It would be an interesting exercise to study about the effect of Ayurvedic treatment in influencing the misfolding of alpha synuclein protien as well as its migration from the gut to the brain. It would also be interesting to see if Ayurvedic treatments can restore the balance of the microbiome in the gut of patients afflicted with Parkinson’s Disease.

Careful documentation of cases of Parkinson’s Disease treated with Ayurvedic interventions highlighting and correlating the treatment protocol with clinical improvements will be a very important first step in this direction.

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