Adult stem cell therapy has shown great promise at regenerating the central nervous system in general. In Parkinson’s disease in particular, the dopamine producing neurons that die are responsible for connecting a structure in the brain called the substantia nigra to another structure called the striatum, which is composed of the caudate nucleus and the putamen. Such “nigro-striatal” neuronal connections allow for the release and transfer of the chemical transmitter dopamine onto their target neurons in the striatum, which controls body movement. These dopamine producing neurons can be replaced with stem cell transplantation.
As previously described, it is the degeneration of these dopamine producing neurons which results in Parkinson’s disease. Logically, therefore, it is the regeneration of these same dopamine producing neurons which restores normal body movement and reverses the symptoms of Parkinson’s disease. Adult stem cells have been shown to be effective at this regeneration, with the neuronal connections re-established well into the striatum.
Cell transplantation therapies have been used to treat certain neurodegenerative diseases such as Parkinson’s and Huntington’s disease. However, ethical concerns over the use of fetal tissues (embryonic stem cells), and the inherent complexities of standardising the procurement, processing and transplantation methods of this tissue, have prompted the search for a source of cells that have less ethical stigmatisations, are readily available and can be easily standardised. Several sources of human cells that meet these principles have been under investigation.
Stem cells from human umbilical cord blood are one source that is consistent with these principles; therefore, they have become of great interest in the field of cellular repair / replacement for the treatment of CNS diseases, neurodegenerative diseases and injury. Furthermore, umbilical cord stem cells are easily available and less immunogenic compared to other sources for stem cell therapy such as bone marrow.
It is neither necessary nor advisable to use embryonic stem cells in such a therapy, since adult stem cells carry the required pluripotency to differentiate into neurological tissue; adult stem cells lack the risk of forming teratomas (tumors) which have always been the identifying feature of embryonic stem cells. Ethics and politics aside, purely from a scientific perspective, the characteristics and behaviour of adult stem cells are highly preferable to those of embryonic stem cells.
The ability of umbilical cord blood stem cells to treat these neurodegenerative diseases may be attributed to the inherent ability of stem cell populations to replace damaged tissues. Alternatively, various cell types within the graft may promote neural repair by delivering neural protection and secretion of neurotrophic factors.
Even within the brain itself, the white matter is known to contain multipotent progenitor cells that are able to differentiate into all the major cell types of the brain, including neurons. Scientists are therefore hoping to discover additional ways in which to stimulate the brain’s own stem cells for localised repair and regeneration.
Specific stem cells have been discovered in two locations within the adult primate brain, namely, in the subventricular zone and in the dentate gyrus of the hippocampus. In the 1990s, researchers discovered that stem cells from these two areas of the brain are naturally mobilized and stimulated automatically to migrate toward a site of injury, whenever the brain incurs damage.
Stem cell transplantation / replacement has emerged as the novel therapeutic strategy for Parkinson’s disease. Stem cells offer the potential to provide a virtually unlimited supply of optimized dopamine producing neurons that can provide enhanced benefits. Stem cell treatments have now been shown to be capable of differentiating into dopamine neurons that provide benefits following transplantation in animal models of Parkinson’s disease.
There have been numerous advances in enhancing the yield of dopamine producing neurons from stem cells, and promoting their survival and consequent clinical effects. As Parkinson’s disease involves degeneration of both dopaminergic (dopamine producing) and non-dopaminergic neurons, it also remains to be determined if transplantation of even the ideal dopamine producing neuron will improve non-dopaminergic features of the disease or provide benefits superior to existing therapies.
Clinical trials with transplanting dopamine producing tissue have provided evidence that stem cell transplantation could be a viable alternative to current traditional treatments.
The stem cell transplantation in the animal model of Parkinson’s disease proves that it is capable of relieving symptoms and restoring damaged brain function. Future stem cell research should focus not only on ameliorating the symptoms of Parkinson’s disease but also on neuroprotection or neurorescue that can favorably modify the natural course and slow the progression of the disease. Some of these cells have been the subject of clinical trials, which to date have produced variable outcomes. Therefore, whilst cell therapies remain a promising treatment for Parkinson’s disease, there is need for further refinement of the techniques involved in this procedure.
Parkinson’s disease belongs to a group of conditions called motor system disorders, which are the result of the loss of dopamine producing brain cells. The four primary symptoms of Parkinson’s disease are tremor, or trembling in hands, arms, legs, jaw, and face; rigidity, or stiffness of the limbs and trunk; bradykinesia, or slowness of movement; and postural instability, or impaired balance and coordination. As these symptoms become more pronounced, patients may have difficulty walking, talking, or completing other simple tasks. Parkinson’s disease usually affects people over the age of 50.
Early symptoms of Parkinson’s disease are subtle and occur gradually. In some people the disease progresses more quickly than in others. As the disease progresses, the shaking, or tremor, which affects the majority of Parkinson’s disease patients may begin to interfere with daily activities. Other symptoms may include depression and other emotional changes, difficulty in swallowing, chewing, and speaking, urinary problems or constipation, skin problems and sleep disruptions.
There are currently no blood or laboratory tests that have been proven to help in diagnosing sporadic Parkinson’s disease. Therefore the diagnosis is based on medical history and a neurological examination. The disease can be difficult to diagnose accurately. Doctors may sometimes request brain scans or laboratory tests in order to rule out other diseases.
At present, there is no cure for Parkinson’s disease, but a variety of medications provide dramatic relief from the symptoms. Usually, patients are given levodopa combined with carbidopa. Carbidopa delays the conversion of levodopa into dopamine until it reaches the brain. Nerve cells can use levodopa to make dopamine and replenish the brain’s dwindling supply. Although levodopa helps at least three-quarters of Parkinson’s disease cases, not all symptoms respond equally to the drug. Bradykinesia and rigidity respond best, while tremor may be only marginally reduced. Problems with balance and other symptoms may not be alleviated at all. Anticholinergics may help control tremor and rigidity.
Other drugs, such as bromocriptine, pramipexole, and ropinirole, mimic the role of dopamine in the brain, causing the neurons to react as they would to dopamine. An antiviral drug, amantadine, also appears to reduce symptoms. In May 2006, the FDA approved rasagiline to be used along with levodopa for patients with advanced Parkinson’s disease or as a single-drug treatment for early Parkinson’s disease.
In some cases, surgery may be appropriate if the disease doesn’t respond to drugs. A therapy called deep brain stimulation (DBS) has now been approved by the U.S. Food and Drug Administration. In DBS, electrodes are implanted into the brain and connected to a small electrical device called a pulse generator that can be externally programmed. DBS can reduce the need for levodopa and related drugs, which in turn decreases the involuntary movements called dyskinesias that are a common side effect of levodopa. It also helps to alleviate fluctuations of symptoms and to reduce tremors, slowness of movements, and gait problems. DBS requires careful programming of the stimulator device in order to work correctly.
Parkinson’s disease is both chronic, meaning it persists over a long period of time, and progressive, meaning its symptoms grow worse over time. Although some people become severely disabled, others experience only minor motor disruptions. Tremor is the major symptom for some patients, while for others tremor is only a minor complaint and other symptoms are more troublesome. No one can predict which symptoms will affect an individual patient, and the intensity of the symptoms also varies from person to person.
The National Institute of Neurological Disorders and Stroke (NINDS) conducts Parkinson’s disease research in laboratories at the National Institutes of Health (NIH) and also supports additional research through grants to major medical institutions. Current research programs funded by the NINDS are using animal models to study how the disease progresses and to develop new drug therapies. Scientists looking for the cause of Parkinson’s disease continue to search for possible environmental factors, such as toxins, that may trigger the disorder, and study genetic factors to determine how defective genes play a role. Other scientists are working to develop new protective drugs that can delay, prevent, or reverse the disease.
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