yulius hermanto
Stem Cells Research in Parkinson Disease
Introduction
The increased of life expectancy has brought to us a new health problem. The increasing of degenerative diseases has become health burden. Because of that scientist look for another option in treating those diseases. In this article, I will focus on Parkinson Disease.
The possibility of repairing and replacing the damaged human brain has been a dream of physicians and scientists for decades. Parkinson disease is a natural first when it comes to tackling this ambitious feat, primarily because the majority of the signs and symptoms appear to result from the progressive loss of cells in a small area known as the substantia nigra, which sits atop the brain stem. These cells (substantia nigra) produce dopamine, which is delivered to part of brain known as the striatum.
When the nigral neurons die, and striatal dopamine depletes, Parkinson Disease occurs, recognized by the signs and symptoms. Therefore, replacing missing neurons in a limited area of the brain should in theory reverse parkinsonism, making this an attractive approach. But the challenge of actually replacing injured and/or lost neurons in the adult human nervous system has proven to be a daunting task with far more bumps in the road, both political and scientific, than anyone would have anticipated.
Neurotransplantation: Stem Cell Approach
Stem cell therapy is in the forefront when talking about tissue repair and regeneration. Its potencial for tissue repair and replacement are being considered as an approach to treat neurodegenerative diseases such as Parkinson Disease, ALS, Multiple Sclerosis, etc.
Stem cell therapy has already reached human trial in Parkinson disease, including the use of both adult adrenomedullary tissue and human fetal mesencephalic tissue (which is rich in dopaminergic neurons); the lessons learned should not be ignored. While adrenomedullary transplantation proved to be failed with little efficacy and unacceptable morbidity and mortality, a number of the early open label trials with human fetal mesencephalic tissue appeared to be very promising. The usage of human fetal tissue put ethics pro and cons about it.
However, some trials failed to show a significant clinical benefit based on their primary endpoint variables in spite of substantial evidence of graft survival based on both autopsy and imaging studies. Unfortunately, a substantial subset of patients also developed persistent excessive movements known as dyskinesias. Dyskinesias are typically a consequence of long-term L-dopa therapy, but in the patients receiving transplants, these movements persisted even after L-dopa was discontinued, raising serious safety concerns.
The Possible Explanations
There are a lot of theories that being proposed but the reality still unknown. Theories range from poor graft survival to the possibility that low-grade inflammation interfered with graft function. With regard to Parkinson disease, the first task has been to create authentic Dopaminergic neurons cell lines that can be used to replace the missing neurons in the nigrostriatal system, and the second to get those cells to persist in vivo without forming tumors. While this has been an intensive area of research, there are only a limited number of successes so far, and these have been achieved primarily in rodents.
To date, almost all fetal cell transplants have involved putting these cells into the striatum as have most experimental studies. However, it is still not clear that this is the best target area; it is also possible that it will be necessary to transplant the cells to multiple sites, including the substantia nigra. The major challenge at the current time appears to be getting transplanted Dopaminergic embryonic stem cells to maintain their phenotype in large numbers and over a prolonged period of time.
Regardless of whether or not this proves to be the case, it can be hoped that this new initiative will serve as a beacon of hope for scientists and patients alike as we press ahead in this challenging area of science that appears to promise so much for the treatment of human diseases.
The increased of life expectancy has brought to us a new health problem. The increasing of degenerative diseases has become health burden. Because of that scientist look for another option in treating those diseases. In this article, I will focus on Parkinson Disease.
The possibility of repairing and replacing the damaged human brain has been a dream of physicians and scientists for decades. Parkinson disease is a natural first when it comes to tackling this ambitious feat, primarily because the majority of the signs and symptoms appear to result from the progressive loss of cells in a small area known as the substantia nigra, which sits atop the brain stem. These cells (substantia nigra) produce dopamine, which is delivered to part of brain known as the striatum.
When the nigral neurons die, and striatal dopamine depletes, Parkinson Disease occurs, recognized by the signs and symptoms. Therefore, replacing missing neurons in a limited area of the brain should in theory reverse parkinsonism, making this an attractive approach. But the challenge of actually replacing injured and/or lost neurons in the adult human nervous system has proven to be a daunting task with far more bumps in the road, both political and scientific, than anyone would have anticipated.
Neurotransplantation: Stem Cell Approach
Stem cell therapy is in the forefront when talking about tissue repair and regeneration. Its potencial for tissue repair and replacement are being considered as an approach to treat neurodegenerative diseases such as Parkinson Disease, ALS, Multiple Sclerosis, etc.
Stem cell therapy has already reached human trial in Parkinson disease, including the use of both adult adrenomedullary tissue and human fetal mesencephalic tissue (which is rich in dopaminergic neurons); the lessons learned should not be ignored. While adrenomedullary transplantation proved to be failed with little efficacy and unacceptable morbidity and mortality, a number of the early open label trials with human fetal mesencephalic tissue appeared to be very promising. The usage of human fetal tissue put ethics pro and cons about it.
However, some trials failed to show a significant clinical benefit based on their primary endpoint variables in spite of substantial evidence of graft survival based on both autopsy and imaging studies. Unfortunately, a substantial subset of patients also developed persistent excessive movements known as dyskinesias. Dyskinesias are typically a consequence of long-term L-dopa therapy, but in the patients receiving transplants, these movements persisted even after L-dopa was discontinued, raising serious safety concerns.
The Possible Explanations
There are a lot of theories that being proposed but the reality still unknown. Theories range from poor graft survival to the possibility that low-grade inflammation interfered with graft function. With regard to Parkinson disease, the first task has been to create authentic Dopaminergic neurons cell lines that can be used to replace the missing neurons in the nigrostriatal system, and the second to get those cells to persist in vivo without forming tumors. While this has been an intensive area of research, there are only a limited number of successes so far, and these have been achieved primarily in rodents.
To date, almost all fetal cell transplants have involved putting these cells into the striatum as have most experimental studies. However, it is still not clear that this is the best target area; it is also possible that it will be necessary to transplant the cells to multiple sites, including the substantia nigra. The major challenge at the current time appears to be getting transplanted Dopaminergic embryonic stem cells to maintain their phenotype in large numbers and over a prolonged period of time.
Regardless of whether or not this proves to be the case, it can be hoped that this new initiative will serve as a beacon of hope for scientists and patients alike as we press ahead in this challenging area of science that appears to promise so much for the treatment of human diseases.
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