A recent article in the December, 2012 issue of Stem Cells by Chen and Burton-Jones describes potential stem cell treatments for Alzheimer's disease (AD), as well as the use of stem cells to model and investigate the disease. They offer encouraging information on how stem cells might play a part in future therapy, based on a number of past and ongoing research studies.
Alzheimer's disease is the most common type of age-related dementia that affects over 5 million people in the U.S., with projections that 115 million people worldwide may develop dementia by the year 2050. Current treatment modalities provide no long-term benefits, even after extensive research for many years.
Stem cell treatment options have been under investigation using animal studies, with some enlightening findings so far. For the majority of diseases and disorders that are treated with stem cells, the therapy is aimed at replacing missing or degenerative cells with new ones. In the case of AD, that type of treatment would not be likely to produce a benefit, as a number of neuronal systems and neurotransmitter phenotypes can be affected and cell replacement would not be viable. Too many types of nerves are involved, along with the complex systems of connectivity, much of which develops in utero. Therefore, cell replacement would not seem to offer benefit with such a diffuse set of problems that are encountered in AD.
So how could stem cells be of benefit? Well, the benefits seem to come through indirect means. One of the problems found in AD is a loss of synapses. This loss seems to correlate most tightly with the dementia process. The number of synapses and their relative strength appears to be closely regulated by a select group of neurotrophins, groups of secreted proteins that induce the development, function, and survival of neurons. These are essentially growth factors for our nervous system. Stem cells can induce high levels of these growth hormones, including brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF). In this way, stem cell therapy might allow for delivery of these proteins to the disease-affected areas of the brain and thus possibly increasing neuronal survival.
Another known factor in AD is chronic inflammation. Stem cells can have anti-inflammatory properties, as certain stem cell populations have been shown to induce the expression of anti-inflammatory factors, specifically interleukin-10 and prostaglandin E2. There are mice studies that have shown improved cognition and improved pathology due to apparent attenuation of the inflammatory process after treatment with stem cells. However, it is not known how this will translate to human patients, if at all, as prior clinical trials with anti-inflammatory drugs have shown no benefit in patients with AD.
Another potential way that stem cells could provide some benefit is by delivering therapeutic proteins to the damaged areas in the brain, as prior studies have shown the ability of stem cells to migrate throughout the brain and focus on regions damaged by injury and/or inflammation. What is not yet known is how much of an effect the underlying pathology plays on this response, as the severity of the disease might influence the likelihood of success, along with unknowns surrounding the lifespan of engrafted cells, the patient's immune response, and even the source of the cells and proteins.
As the excitement grows related to the possibilities, caution must be encouraged as more studies need to be undertaken. Difficulties exist in researching treatment options for AD, as no long term human studies have taken place. Stem cells may prove quite useful in studying the AD process, as stem cell lines can be elicited that exhibit known AD-associated genes. This will allow for researchers to focus on the differences between the normal and pathogenic function of these genes.In this way, stem cells may hold the key to learning more about the disorder and to eventually treating it.
