What You Wanted To Know About Parkinson's Disease

What is a Parkinson's Disease? What causes the disease? How does it affect the people suffering from it? Parkinson's Disease is one of the most common diseases affecting the movement and the neurologic system amongst the elderly. Despite the fact of the motor affection, it is now well known that the effects lie beyond motor abilities, as autonomic functions such as sleep, mood, cognition, gastrointestinal system and some others are also greatly impaired.

First Insights

This disorder was firstly described and recognized as “Shaking Palsy” by Dr. James Parkinson in the early 19^thcentury, although its symptoms had been known for centuries.

What goes wrong in PD? The Central Nervous System is responsible of coordinating the function of the human body, including movement. Therefore, the brain contains certain areas specialized in particular functions. One of the main motor areas is the basal ganglia, in which the dopaminergic neurons are the ones responsible of dopamine production. This special chemical, also called neurotransmitter, is essential for transmitting the impulse to produce the voluntary movement.  

Furthermore, there are some patients with further defects. In these patients, besides the loss of the dopaminergic neurons, some toxic aggregations are present within neurons. These aggregations are called "Lewy Bodies" which are believed to cause damage in the brain. It remains elusive how these aggregations can actually damage the neurons in which they are present.

What causes PD? Parkinson's Disease is a multifactorial disease, meaning that there are several factors involved in its development. About 2-5 percent of the cases are familial because the cause is a defect in a specific gene. Thus, the chance of developing the disease increases from 25-50% depending on the specific defect. 

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Some environmental agents that have been associated as risk factors are pesticides, living in a rural area, working in printing plants, mines, and other chemicals. Diabetes, high fat intake, migraine or severe headaches during midlife, the aging process and lack of activity have been also implicated but there is not enough evidence to prove a direct link with the development of PD.

Crucial Clinical Diagnosis: The Challenge

The main signs and symptoms of PD appear in the  6^th decade of life and in rare cases, mainly familial, the disease develops during early adulthood.

The presence of these symptoms is fundamental for the diagnosis, and they are usually detected several years or even decades after the neuronal death started.

Non-motor symptoms are also an important feature of the disease. The main symptoms are a reduced sense of smell, constipation, visual hallucinations, bladder frequency and/or urgency, dribbling of saliva, mood affection and dementia. Patients with PD start to develop these non-motor features before the motor stage appears.

Diverse clinical presentation in some patients with Parkinson's complicate the clinical diagnosis and most of the time the appropriate therapy is not applied. Sadly, in some cases, the definitive diagnosis is post-mortem by studying the patient's brain.

Parkinson's Disease Nowadays: New Tests, Prevention And Better Treatments

PD is not an easy disease to detect, treat and handle, both by the specialist and the patient. However, researchers have made very impressive advances in the detection of the disease, as well as in elucidating the mechanisms that could be driving dopaminergic neurons to degenerate and cause the symptomatology seen in this neurodegenerative problem. One of these advances is certainly the detection of the defective gene and prevention therapies for people carrying this defect.

Genetics And Prevention

When a familial history of Parkinson's Disease is present, the genetic diagnosis is crucial for a proper genetic counseling, follow-up, prognosis and diagnosis in their relatives. Unfortunately, it is only available to detect the cause in a few cases due the rarity of the cases and known genetic causes. However, modern techniques have been developed and more genetic causes have been and will be revealed.

Vitamin E has also been linked to dopaminergic neurons protection, acting as either a neuro-protector or by delaying the symptoms. Deficit of vitamin D has also been associated with progression of the disease and its supplementation seems to improve the symptoms in some clinical trials. Their actual protective effect remains to be further proved and elucidated.

Current Treatment And Future Research

Since the lack of dopamine is the prominent feature, it can be substituted by a synthetic chemical called levodopa, in order to restore the deficit. However, despite improving symptomatology at the beginning, at a long term the treatment is not effective. Besides this, chronic exposure to levodopa leads to toxicity and worsening of the symptoms.

Since Parkinson's Disease is a progressive disorder in which the neuronal loss cannot be restored, current treatments are not effective, so research is focused in developing a better treatment that can diminish the neuronal death and restore their function.

New treatments designed to improve and/or restore the function have been developed. 

Follow-up of these patients showed an improvement in motor functions, which reflected in a better quality of life, when compared to patients taking the pharmacological treatment. However, long term assessment is needed to clarify the true benefits of this therapy for the majority of the patients.

Gene therapy has been greatly explored and designed. This will provide a stable and better treatment without detrimental secondary effects. The challenge is to design an effective delivery method within the brain without causing damage. So far, a very small number of agents have been tested thus, larger trials should be designed and tested for unknown risks associated to the treatment and its delivery.

Nowadays, new exciting insights in mechanisms leading to neuronal cell death and damage have been studied. Here, hopes of a novel and better therapeutic approach is exciting. However, the existing gap between bench scientist and clinicians affects the development of an effective therapy when tested in clinical trials in patients with Parkinson´s Disease. 

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Parkinson's Disease remains a great challenge for science, where better understanding of the mechanisms of neurodegeneration is crucial, so that better treatment and counselling can be provided to patients suffering from it.