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Potential role of stem cells in the therapeutics for major diseases
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Stem cells could accelerate drug development for Parkinson’s disease

Parkinson’s disease is progressive neuromuscular disorder that (usually) affects people over the age of 50. Most prominent signs of the disease are tremors, trembling of legs, arms, jaws, bradykinesia and impaired movement coordination. Since disease is progressive, most patients eventually loss ability to complete their usual daily activities and require special care. Parkinson’s disease affects both sexes, but men have slightly higher chance to develop disease. People all around the world suffer from Parkinson’s disease. It is estimated that 7 to 10 million people throughout the world live with the disease. Just in USA over million people is diagnosed with Parkinson’s disease, and this number overcome total number of all USA patients diagnosed with Lou Gehrig’s disease, multiple sclerosis and muscular dystrophy. Parkinson’s disease is expensive, both for the patients and for the economy of the country that supports the patients. Estimated individual cost are around 2500 dollars per year, but surgical interventions can rise the price to 100 000 dollars per person. Special care, medications and inability of patient to work, cost economy of USA 25 million dollars per year. At the moment, there is no cure for Parkinson’s disease; few medications are used to alleviate the symptoms of the disease. Main goal of various scientists around the world is to find a drug that could stop disease progression.

Parkinson’s disease develops sporadically or as consequence of mutated genes. Around 15% of Parkinson’s cases are inherited (already recorded cases of disease in family), and the rest of the cases are result of still unclear combination of environmental and genetic factors. Part of the brain affected by the disease is substantia nigra, where dopaminergic neurons are located. These neurons release dopamine and induce smooth muscle movements. When 50-80% of these neurons die, loss of muscle control and impaired movement in general will become obvious.

Latest experiments with stem cells could accelerate development of efficient treatments for Parkinson’s disease. Those cells allow scientists to track disease development and its progression directly in a dish. Skin cells isolated from patients will be transformed into induced pluripotent stem cells or iPS, using several (in normal circumstances silent) transcription factors that will reverse adult cell to the pluripotent stage. When this phase is accomplished, stem cells will be guided to mature into neuronal cells. Healthy cells will be turned into typical Parkison's neurons so that impaired cellular processes and potential beneficial effect of new or already known drugs could be studied. Neuronal cells in Parkinson’s disease show impaired function of the mitochondrial system: altered energy production, sensitivity toward oxidative stress and increased sensitive to various toxins which normal mitochondria would survive. Although several genetic mutation located at 17 different location within the genome are associated with Parkinson’s disease, only couple of genes are closely examined. Two well examined mutated genes are LRRK2 and PINK1 and they are usually found in the patients with already noted cases of disease in family. Mitochondrial function is closely associated with LRRK2 and PINK1 genes; it was noted that oxygen consumption rate (turnover of glucose to energy) is lower in patients with mutated LRRK2 gene and higher in patients with mutation in the PINK1 gene. Mitochondria shows higher vulnerability toward oxidative stress in PINK1 mutated cells compared to LRRK2 cells. Both type of cells showed sensitivity toward toxins. Cells exposed to toxin were treated with few drugs to assess their potential to reverse toxic effect. Oxidative stress in the cells is normally prevented by antioxidants. Coenzyme Q10 is used in treatment of Parkinson’s disease and when tested in the dish, neurons carrying both types of mutations showed beneficial response. Rapamycin is immunosuppressant that could delay onset of neurodegenerative disorders such as Alzheimer’s disease. After exposing neuronal cells to rapamycin, only cells carrying LRRK2 mutation showed beneficial effect; rapamycin didn’t show any effect on PINK1 cells. This type of experiments showed that different types of mutations result in specific types (subgroups) of disease and that drug efficiency depends on genetic background of each patient.

Analysis of genetic background provides more information on disease type and could lead to personalized treatment of Parkinson’s disease. Although ideal treatment is still far away, stem cells in the research of Parkinson’s disease could improve future treatment options.
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RE: Potential role of stem cells in the therapeutics for major diseases - by BojanaL - 01-25-2013, 08:17 PM
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