In the last few years, two significant scientific milestones have emerged. The first was the finding of the existence of central nervous system neural stem cells. This has led to a new way of thinking about the brain, as previously scientists believed the brain was not capable of regeneration. And the second was the isolation, expansion and manipulation of human stem cells.
In neurological disorders where cells are lost focally such as in Parkinson’s disease, the use of stem cells to treat the accompanying symptoms is thought to have great potential. However, the greater extent of neuronal cell loss in dementia, and in Alzheimer’s disease in particular, means that the use of stem cell therapy for the treatment of Alzheimer’s disease is less well understood. There are numerous reports of improvements in functioning in Alzheimer’s disease following stem cell treatments; these remain unverified, however. For this reason Tissu intends to document all its results.
If neurons that are lost can be replaced then it is assumed that mental deterioration can be halted and possibly reversed. Tissu carefully assesses which cells are used for stem cell treatment and for this reason our approach is to use stem cells that have commenced differentiation into adult neural stem cells for Alzheimer’s disease. The use of adult mesenchymal stem cells is of great benefit, overcoming ethical issues and problems of possible immune reaction.
Currently there are no medicines that can slow the progression of Alzheimer’s disease. However, four FDA-approved medications are used to treat Alzheimer’s disease symptoms. These drugs help individuals carry out the activities of daily living by maintaining thinking, memory, or speaking skills. They can also help with some of the behavioral and personality changes associated with Alzheimer’s disease. However, they will not stop or reverse the process and appear to help individuals for only a few months to a few years. Donepezil (Aricept), rivastigmine (Exelon), and galantamine (Reminyl) are prescribed to treat mild to moderate Alzheimer’s disease symptoms. Donepezil was recently approved to treat severe Alzheimer’s disease as well. The newest Alzheimer’s disease medication is memantine (Namenda), which is prescribed to treat moderate to severe Alzheimer’s disease symptoms.
So it would seem that the brain has the capability to repair itself. Experiments in animal models of Alzheimer’s disease and Parkinson’s disease have shown that there is an up-regulation in number and subsequent migration of neural stem cells from the subventricular zone to the disease area. Also, a recent study has provided the first evidence that regenerative mechanisms may be active in the adult human brain in response to trauma or neurodegenerative processes. Post-mortem analysis of the hippocampus in a small cohort of Alzheimer’s disease patients indicated a significant increase in neurogenesis and the more severely affected patients displayed the most significant increases in newly generated hippocampal neurons. This endogenous neural stem cells ‘movement’ may be a mechanism to the neuronal degeneration in all these conditions that may lead to an improvement in patients functioning.
Alzheimer’s disease is an age-related, degenerative chronic brain disorder that develops over a period of years. Initially, people experience memory loss and confusion, which may be mistaken for the kinds of memory changes that are sometimes associated with normal aging. However, the symptoms of Alzheimer’s disease gradually lead to behavioural and personality changes, a decline in cognitive abilities such as decision-making and language skills, and problems recognizing family and friends. Eventually this leads to a severe loss of mental function. These losses are related to the worsening breakdown of the connections between certain neurons in the brain and their eventual death.
It is the most common cause of dementia among people age 65 and older. In dementia, neurons are lost throughout the brain - for example, the cortex, especially its frontal, parietal and temporal areas, the basal ganglia and the hippocampus - resulting in a general mental deterioration. If these neurons could be replaced it is hypothesised that mental deterioration could be halted and possibly reversed. Stem cell treatments provide a potential means of accomplishing this goal. Stem cell treatments may also therefore help senile dementia.
There are three major abnormalities in the brain that are associated with the disease process of Alzheimer’s:
In a very few families, people develop Alzheimer’s disease in their 30s, 40s, and 50s. This is known as “early onset” Alzheimer’s disease. These individuals have a mutation in one of three different inherited genes that causes the disease to begin at an earlier age. More than 90 percent of Alzheimer’s disease develops in people older than 65. This form of Alzheimer’s disease is called “late-onset” Alzheimer’s disease, and its development and pattern of damage in the brain is similar to that of early-onset Alzheimer’s disease. The course of this disease varies from person to person, as does the rate of decline. In most people with Alzheimer’s disease, symptoms first appear after age 65.
We don’t yet completely understand the causes of late-onset Alzheimer’s disease, but they probably include genetic, environmental, and lifestyle factors. Although the risk of developing Alzheimer’s disease increases with age, Alzheimer’s disease and dementia symptoms are not a part of normal aging. There are also some forms of dementia that aren’t related to Alzheimer’s disease, but are caused by systemic abnormalities in the small blood vessels and other disease processes.
In conclusion, stem cells provide a very appealing approach for the treatment of neurodegenerative diseases and brain injury. There have been many groundbreaking studies highlighting their exciting therapeutic opportunity, but there are still numerous hurdles that need to be overcome.
Studies have demonstrated that aged animals show significant improvements in cognitive function and neurogenesis after brain transplantation of human neural stem cells or of human adult mesenchymal stem cells that have been dedifferentiated down neural pathways.
Researchers have shown for the first time that putting two specific types of neural cells directly into an aging brain can kick-start creation of brain cells linked to learning and memory.
It has been shown over the last decade that brain cells replicate, a finding that had run counter to previously accepted dogma. The area where neuron-forming stem cells perform much of this replication is the hippocampus, a part of the brain linked to memory and learning, and an area affected in older people, as well as those with Alzheimer’s disease.
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Stem cells in dementia Dr Antigone EkonomouThe Journal of Quality Research in Dementia, Issue 1
Dr Antigone Ekonomou Postdotoral Research Assistant, King’s College London, The Wolfson CARD, The Wolfson Wing, Hodgkin Building, Guy’s Campus, London SE1 1UL.
Alzheimer’s Association: www.alzheimers.org.uk
