Parkinson's Disease
Parkinson’s disease is a nervous system disease which falls into the category of motor system diseases or movement disorders due to it primarily affecting motor control and movement. The disease is attributed to the malfunction of the substantia nigra and basal ganglia. The substantia nigra being a layer of large pigmented nerve cells in the midbrain that produce dopamine and whose destruction is associated with Parkinson's disease itself. Dopamine is one of the brain chemicals involved in the control of physical movement, and Parkinson’s is characterized by dopamine depletion. The basal ganglia being a group of nuclei which contain a rich array of neurotransmitters and receptors controlling muscular movements. Therefore, as these cells are lost, the symptoms that become apparent are generally disorders of movement and its initiation. Common symptoms that are classic for Parkinson's disease include tremor, rigidity and slowed movements and others (2010). Dopamine, found in the basal ganglia, is the neurotransmitter responsible for the dampening effect of the motor signal. If the dampening effect should become too strong, then another neurotransmitter, it is counteracted the effects of the dopamine, thus maintaining a balance in the force of the signals sent to the muscle.
Parkinson’s disease is named for English physician and geologist James Parkinson who lived in 1755 to 1824. His description of the various manifestations of the disease was published in 1817, in a work he himself entitled "An Essay on the Shaking Palsy." In fact, “He used the terms "shaking palsy" and "paralysis agitans" to describe a group of related symptoms, which he carefully observed and recorded” (The Gale Encyclopedia of Science, 2011). Furthermore, Parkinson wrote. "It now seldom leaves him for a moment; but even when exhausted nature seizes a small portion of sleep, the motion becomes so violent as not only to shake the bed-hangings, but even the floor and sashes of the room" (2006). It is now known that this neurological disorder is caused by damage to the brain.
In Parkinson disease, degeneration of the basal ganglia, along with damage to the dopamine-producing cells of the substantia nigra, hinders the proper functioning of the nerve pathway that controls movements of the muscles. The muscles become excessively tense, a condition that gives rise to tremor and a rigid joint action. The movements of the body also begin to slow down because of this malfunction. The underlying causing factors that lead to Parkinson's disease are unclear (2010). The cause is probably multi-factorial, meaning that there are several factors which contribute to its development. Clues to the causes of Parkinson's disease can be found in the risk factors which are associated with the disease. Although most cases occur at irregular intervals, there does seem to be some genetic predisposition. Also, people with a close relative with the disease are slightly more likely to develop the disease themselves. Not to mention, it is known that older age and male gender are risk factors as the risk increases with age and is higher in men than women. Parkinson's primarily affects older individuals and its effects increases with age. There may also be some toxins or viruses, exposure to which may increase one's risk for Parkinson's.
Although the actual initial causes of Parkinson's Disease are unknown, the actual process of Parkinson’s disease that occurs in the brains of patients is well known. For unknown reasons, abnormal clumps of protein build up in certain neurons in the brain. These clumps of protein are called Lewy Bodies (2011). As the disease progresses, neurons in certain parts of the brain begin to die. One of the most noticeable areas of damage in this disease is in a group of cells in the substantia nigra. These cells normally use dopamine as their neurotransmitter and are part of the basal ganglia. The death of these dopamine-secreting cells in the brain lead to imbalance and dysfunction of the basal ganglia, affecting motor system control. This imbalance is progressive and would explain why the motor symptoms that are common in patients with Parkinson's disease occur. Although the cells of the substantia nigra is the most profoundly affected early, other areas of the brain can become affected with time, leading to imbalance in other systems and with other neurotransmitters, leading to other late symptoms such as dementia and dysfunction of the autonomic nervous system.
Concerning the diseases symptoms, "symptoms of the disease begin to show when patients are in their 40s, but in the majority of cases most symptoms appear occur after age 50 years" (The Gale Encyclopedia of Science, 2011). At the beginning of the illness, one side of the body may begin to display symptoms such as uncontrollable shaking and tremor. Eventually, the disorder progresses and spreads to both sides of the body. At first, there are signs in basic movement that show difficulty such as in walking, standing, and sitting down. These movements seem strenuous and become difficult to perform. Body movements also slow down, and require much concentration to be performed. The muscles in the body that are at rest become so tense that they end up becoming rigid. Simple facial movements become difficult to perform because of the rigidity. The face often becomes expressionless. It also important to note that instead of the natural arm swing that occurs during movement, stop and the arms hang limply at the side.
Like previously stated, most cases of Parkinson's Disease are sporadic. This means that there is a spontaneous and permanent change in nucleotide sequences (2010). Sporadic mutations also involve unknown environmental factors in combination with genetic abnormalities. The abnormal gene or mutated gene will create an altered protein which will then cause abnormalities in specific areas in the body where the protein is used. In fact, "Familial cases of Parkinson disease can be caused by mutations in the LRRK2, PARK2, PARK7, PINK1, or SNCA gene" (GHR, 2010). These gene mutations appear to disturb the cell machinery that breaks down (degrades) unwanted proteins in dopamine-producing neurons. As a result, undergraded proteins accumulate which lead to the impairment or death of these cells. As a byproduct of energy production, mitochondria make unstable molecules called free radicals that can damage cells. Cells normally counteract the effects of free radicals before they cause damage, but mutations can disrupt this process. In most cases of Parkinson disease, protein deposits called Lewy bodies appear in dead or dying dopamine-producing neurons. It is unclear whether Lewy bodies play a role in killing nerve cells or if they are part of the cells' response to the disease but it may cause parkonism.
Surgical procedures to inactivate certain areas of the brain have sometimes been helpful in restoring movement for some Parkinson's Disease patients who have stopped responding to other medical therapies. While symptoms may be dramatically relieved, the outcome of the treatment is still being studied. Deep brain stimulation is also used as a surgical method to treat the disease. For example, surgical gene therapy for Parkinson's disease led by Professor Matthew During, is one of a series of breakthroughs for his research career and he has been able to take big step towards it becoming an established treatment. In fact, "A recently reported phase two trial found reduced symptoms in patients who received the treatment, compared with others who had sham surgery" (New Zealand Herald, 2010). The treatment was performed under local anesthetic, and involved boring a hole through the skull in order to deliver the genes through a safe virus in a liquid. Professor During led development of the therapy and said that although the trial had not yet been reported in a peer-reviewed journal, it was a milestone. Another possible solution can be gene therapy for Parkinson's Disease. Parkinson’s disease presents several features that would make it ideal for gene therapy. The cause of the major motor symptoms is well defined, and associated with dysfunctions in brain nuclei that can be effectively targeted using technology for gene transfer to brain cells. Therefore, part of the gene therapy strategy would be to aim at increasing the efficacy and at reducing the side effects of the current pharmacological and surgical treatments (2010). Gene therapy aims at treating diseases by genetically modifying the specific genes that are either functionally impaired or capable of relieving the disease symptoms. These genetic modifications can either increase or reduce the expression of specific genes and restore the normal function of the product of these genes. This would decrease the affects of Parkinson's and make for a possible cure for the disease itself.