Therapeutic Use of Stem Cell for Treatment of Parkinsons Disease - Essay Example

Therapeutic Use of Stem Cell for Treatment of Parkinson’s Disease ABSTRACT Research on stem cells has provided enough evidence of making them uniquely situated to treat a broad spectrum of human diseases. The ability of stem cells to participate in brain repair particularly in the case of Parkinson's disease has been increasingly demonstrated in recent studies. Scientists are now able to produce neurons and glia successfully from stem cells in culture. Besides, the use of genetic engineering with stem cell therapies can halt the further degenerative process and can serve as a powerful therapeutic tool. Hence, there is hope for patients with these diseases and can gain from stem-cell-based transplantation therapies. Introduction Parkinson's disease is a very common neurodegenerative disorder that tends to present late in life. It is a disease with a lifetime incidence of 2.5% and a prevalence of at least 2% in individuals over 65 - 70 years of age. Millions of humans are victims of this neurodegenerative disease [1]. It is caused by a progressive degeneration and loss of nigrostriatal dopamine-containing neurons. Sometimes degeneration also occurs in systems of non-dopaminergic neurons [2]. The common symptoms of Parkinson's disease are tremor, rigidity, and hypokinesia (abnormally decreased mobility). Together with these problems various degrees of cognitive, autonomic, and psychiatric abnormalities may also be present [1]. The dopaminergic neurons have their cell bodies located in the substantia nigra pars compacta (SNpc). These special neurons send axons to the caudate and putamen which is collectively known as the corpus striatum. The gradual degeneration of these cells initiates a chain of disorders. Degeneration results in the ongoing decrease over time of striatal dopamine levels which is very essential for normal functioning. This in turn produces a decline in striatal output to the thalamus. These alterations result in a decrease in cortical motor output. This decrease can account for some of the observed motor symptoms, particularly bradykinesia and rigidity, but other features such as a resting tremor probably have a largely non-dopaminergic component [1]. Till date there are several treatments available for Parkinson’s disease however medical science has failed to find a complete cure for this disease. Treatments involving drugs target the dopaminergic nigro-striatal pathway. Unfortunately, it is found that over time the efficacy of these medications is limited by the development of profound motor fluctuations and dyskinesias[1]. The common drug is the oral administration of l-dopa and dopamine receptor agonists, and deep-brain stimulation in the subthalamic nucleus. These treatments are effective for some symptoms, but are associated with side effects and do not stop the progression of the disease [2]. Therapies that completely cure patients of Parkinson's disease is yet to be found, but stem cell therapies offer exciting possibilities [1, 3]. Stem cells have the incredible potential to develop into many different cell types in the body. Serving as a sort of repair system for the body, they can theoretically divide without limit to replenish other cells as long as the person is alive. To be clinically competitive, a stem-cell-based therapy must lead to long-lasting, significant improvement in mobility, ameliorate currently intractable symptoms, or counteract disease progression. Besides, to make stem-cell therapy work, dopaminergic neurons with the characteristics of substantia nigra neurons must be produced in large numbers [1]. Today, stem cell-based therapies might be a turning point in medical science that might represent in the near future a plausible alternative strategy in these disorders. However, it is important to consider the challenges before envisaging any human applications of stem cell-based therapies in neurological diseases. For instance, the questions such as which is the ideal stem cell source for transplantation, what are the most appropriate route of stem cell administration, and, last but not least, which is the best approach to achieve an appropriate, functional, and long-lasting integration of transplanted stem cells into the host tissue. The answers to these questions can indeed contribute to a significant knowledge on treating Parkinson’s disease [4]. According to Lindvall for Parkinson's disease four different cellular sources could be used to form dopaminergic neurons for neural transplantation. These include (i) embryonic stem cells from a fertilized egg; (ii) neural stem cells from an embryonic brain; (iii) neural stem cells from an adult brain; or (iv) stem cells from other tissues. However, further research is required to find out the crucial issue whether the transplanted cells would form functional dopaminergic neurons, regardless of the source of the stem cells [3]. The basic understanding that the adult nervous system develops from multipotential stem cells and that cells with stem-like properties are retained in the adult central nervous system (CNS) has initiated an intense search for ways to utilize their potential for therapeutic treatments of multiple neurological disorders such as Parkinson's disease [5]. It is assumed that with the progress in scientific research, stem cells could soon be used to treat neurological disorders. The clear-cut mechanisms underlying this process is yet to be established, but are perhaps associated with release of growth factors and other trophic agents into the damaged brain. There is still promising research through genetic stem cell engineering. This technique of genetic engineering could be used to enhance the release of therapeutic factors that may prevent further degeneration of these cells. Targeted delivery of therapeutic agents could be achieved by modifying stem cells to release specific drugs at the site of transplantation. Hence, genetic stem cell engineering might thus constitute promising pharmaceutical approaches to treating diseases of the nervous system. It is predicted that elucidation and exploitation of this new ‘stem cell pharmacology’ has the potential to revolutionise treatment of neurological diseases [6]. Experiments using human embryonic cells have been conducted by various researchers. For instance, ventral midbrain tissue containing dopaminergic neurons extracted from 7 to 8 week old human embryos has proven to be capable of establishing functional synapses, and has given rise to surviving dopaminergic neurons in patients with Parkinson’s disease. As a result patients have shown the alleviation of symptoms [7]. Further, in a double-blind study conducted by Freed et al., 17 out of 20 Parkinson’s disease patients showed long-term survival of dopaminergic neurons [7, 8]. When dopaminergic neurons generated from human embryonic stem cells, were introduced in animal models survival after transplantation has been poor. Hence it is essential to conduct further research before clinical application. Besides, some patients will need implants in several areas of the brain. As a mater of fact in such cases optimum recovery will require a tailor-made grafting procedure based on preoperative imaging. It will also be necessary to develop strategies that hinder disease progression. As discussed earlier through the application of genetic engineering could be used as an additional tool to prevent further degeneration by transplanting human stem cells engineered to express neuro-protective molecules such as glial-cell-line-derived neurotrophic factor (GDNF) [2]. Though practical application of these techniques needs further studies, Parkinson’s disease may be the first disease to be amenable to treatment using stem cell transplantation. This is possible mainly due to the factors such as the knowledge of the specific dopaminergic neurons needed to relieve the symptoms Parkinson’s disease. Above all, several laboratories, research institutions and private agencies have been successful in developing methods to induce embryonic stem cells to differentiate into cells with many of the functions of dopaminergic neurons. However, a lot need to be done when it comes to human beings. Scientists are developing a number of strategies for producing dopamine neurons from human stem cells in the laboratory for transplantation into humans with Parkinson's disease. If these researches lead to the successful generation of an unlimited supply of dopamine neurons through stem cells then neuro-transplantation will be widely available for Parkinson's patients. References 1. Young, H.E. et al. Adult-derived stem cells and their potential for use in tissue repair and molecular medicine, J. Cell. Mol. Med. Vol 9, No 3, 2005 pp. 753-769. 2. Lindvall, O. and Kokaia, Z. Stem cells for the treatment of neurological disorders, Nature Vol 441, 29 June 2006, pp. 1094-1096. 3. Lindvall O. Stem cells for cell therapy in Parkinson's disease. Pharmacol Res. 2003; 47: 279–87. 4. Pluchino, S., Zanotti, L., Deleidi, M and Martino, G. Neural stem cells and their use as therapeutic tool in neurological disorders, Brain Research Reviews 48 (2005), pp. 211–219. 5. Miller, R.H. The promise of stem cells for neural repair, Brain Research Vol. 1091 (2006) pp. 258 – 264. 6. Tai, Yu-Tzu and Svendsen, C.N. Stem cells as a potential treatment of neurological disorders, Current Opinion in Pharmacology 2004, 4: pp. 98–104. 7. Freed CR, Greene PE, Breeze RE, Tsai WY, DuMouchel W, Kao R, Dillon S, Winfield H, Culver S, Trojanowski JQ et al.: Transplantation of embryonic dopamine neurons for severe Parkinson’s disease. N Engl J Med 2001, 344: pp 710-719. 8. Mayhall, E.A., Paffett-Lugassy, N. and Zon, L.I. The clinical potential of stem cells, Current Opinion in Cell Biology 2004, 16: pp 713–720. Read More