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Jack Sisson's TBI Blog
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Friday, May 20, 2011
Cell Replacement Therapy: A Promising but Unproven Approach to Repairing the Parkinson’s Brain
Jack has long been a proponent of stem cell research, and especially embryonic stem cells, whose use has been controversial, with most opposition coming from a moral and/or religious based belief about the beginning of human life. Most opponents to embryonic stem cell research believe human life begins at conception, thus, in their view, it is morally wrong to use embryos for medical research, even though such embryos are often slated for destruction. Whatever one's stance on embryonic stem cells, many scientists believe they offer significant hope for curing many of our most devastating diseases. One example is Parkinson's Disease.
From The Michael J Fox Foundation: Cell replacement therapy seeks to restore function in the body by replacing cells lost due to disease with new, healthy ones. In Parkinson's disease, this means replacing dopamine cells in the brain, the main type of cell that degenerates in the disease. Researchers hope that one day they will be able to use stem cells or iPS cells to successfully engineer healthy new dopamine-producing cells. These healthy cells would then be implanted into the brain, where the cells could in theory restart the brain's production of dopamine and restore normal movement.
At this time scientists are working to overcome two major challenges: first, engineering the dopamine-producing cells (see Stem Cells 101); second, getting these cells to function properly once they are transplanted into the brain. To date, scientists have had the most success generating robust dopamine neurons, in both quantity and quality, using embryonic stem (ES) cells. However, whether these engineered dopamine neurons are sufficiently 'authentic' — that is, whether they express everything natural ones do — is a remaining challenge.
Even if seemingly authentic dopamine neurons can be generated, researchers face an enormous hurdle in coaxing these cells to grow and make the correct connections in a host brain. This involves determining where to place the cell grafts and how to deliver them without causing additional brain damage or triggering immune rejection or inflammatory effects.
Additionally, the new cells must also be able to retain the characteristics of a dopamine neuron once implanted in the brain, where they will be exposed to other factors that may influence their further development and survival. Following transplantation into pre-clinical models, today's engineered cells often do not survive for long, can turn into different cell types or in some cases cause uncontrolled cell growth. For this reason, they are obviously not yet ready for therapeutic use in humans.
-------------------Based on evidence to date, the Foundation believes that the development of viable and feasible cell replacement therapies could revolutionize the treatment of Parkinson's disease. However, the hurdles to success are great; much work remains to be done before cell replacement therapy for PD is a viable therapy for patients. Furthermore, even if all roadblocks are overcome, cell replacement therapy may not be the “silver bullet” for treating PD. For example, researchers feel that dopamine cell replacement might have little or no effect on symptoms of PD not directly related to loss of dopamine cells, such as cognitive dysfunction, sleep problems, depression, constipation and gait and posture problems.
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