Could stem cells repair the damaged brain in Alzheimer’s?
Stem cell therapies may hold the cure to Alzheimer’s, although so far that cure has been elusive. People who suffer from Alzheimer’s disease experience disorientation regarding time and place, changes in mood, personality and behavior, memory loss, difficulty solving problems or planning, and difficulty writing or performing other routine and familiar tasks. This progressive and irreversible brain disorder may affect judgment, initiative and social life, and can lead to physical symptoms such as vision problems.
Alzheimer’s affects mostly people aged 70 years and above, and is more common in women. It is the main risk factor for dementia among the elderly.
There is no known cure for Alzheimer’s. Conventional treatments, both drug-based and non-drug strategies, may help with cognitive and behavioral symptoms, but have little to no effect on the disease’s development over the long term. Current medications can’t stop Alzheimer’s from progressing, but they can temporary lessen symptoms like confusion and memory loss.
Although there have been attempts to find a remedy for Alzheimer’s, and despite the fact that scientists have managed to effectively treat lab animals with drug-based treatments, no animal model has managed to truly mimic its symptoms as they manifest in humans. Remedies that worked in lab animals have failed to work in humans; for this reason, scientists decided to try a different approach by exploring the possibilities of stem cells therapies in Alzheimer’s treatments.
Can Stem cells develop new Alzheimer’s treatments?
Alzheimer’s disease affects neurons in all parts of the brain, and the complexity of this condition makes it difficult to create a model that perfectly mimics its manifestations. At least in theory, stem cells could be used for treating this condition by transplanting neural stem cells into the patient’s brain in an attempt to generate healthy new neurons to replace dead and damaged neurons. It remains unclear whether the brain would be able to integrate the transplanted cells, and if the neural stem cells are able to travel to the damaged areas.
Another great challenge is producing the different types of neurons needed to replace the damaged cells, and to find a way to stimulate the renewal of the lost connections between neural cells. Even if the transplanted cells survive and find their way to the damaged areas, they might become damaged by proteins that build up in the brain—the same proteins that cause the disease in the first place, which means any effects of a stem cell transplant could be only temporary.
A different approach would be to use stem cells for delivering neurotrophins to the brain. Neurotrophin proteins support the growth and survival of neurons, but in patients with Alzheimer’s, they’re produced in amounts too low to contribute such support. Neural stem cells can produce such cells, and in mice tests this method did prove helpful; scientists observed some improvements in memory in mice treated with stem cells.
Mesenchymal stem cells could also be used for treating Alzheimer’s—not to replace damaged neurons, but to heal them. Mesenchymal stem cells may exert anti-inflammatory effects and may help ameliorate the symptoms of Alzheimer’s, but there’s no study at the moment to prove their safety or effectiveness in this condition [3].
Although clinical trials and studies on Alzheimer’s disease treatment to date have a high failure rate, the use of stem cells may be helpful for studying the behavior of brain cells damaged by the condition, as well as for testing various therapeutic approaches and predicting which treatment may help Alzheimer’s patients.
Researchers from the Harvard Stem Cells Institute took skin cells from Alzheimer’s patients and reprogramed them to create induced pluripotent stem cells (iPSC); obtained cells were grown in special lab conditions and were found to release the same proteins that form plaque in Alzheimer’s patients [2]. This may give scientists the opportunity to study the behavior of Alzheimer’s-affected cells and to search for and test new remedies.
Asian scientists managed to turn human fibroblasts into neuronal cells using a chemical cocktail of small molecules [6]. These findings may provide an alternative strategy for modeling the neurodegenerative disorder, which may help scientists understand the mechanisms behind this condition. It may also play an important role in identifying new stem cell based treatments.
References
- http://www.eurostemcell.org/factsheet/alzheimer%E2%80%99s-disease-how-could-stem-cells-help
- http://hsci.harvard.edu/news/alzheimer%E2%80%99s-dish
- http://www.ipscell.com/2012/05/can-stem-cells-be-used-to-treat-alzheimers-disease/
- http://www.sciencedirect.com/science/article/pii/S1934590915003173
- http://www.cell.com/cell-stem-cell/abstract/S1934-5909%2815%2900305-7
- Published in Blog
Could stem cells offer the cure for muscular dystrophy?
The term muscular dystrophy (MD) refers to a group of disorders in which a genetic abnormality causes muscles responsible for controlling movement to become weak, and muscle mass to be lost. These inherited disorders usually affect voluntary (skeletal) muscles, although weakness can also extend to the muscles that control respiration and swallowing.
Given that the genetic mutations triggering MD interfere with the normal production of certain critical proteins, the body is not able to reverse muscle weakening or loss of mass, so even when the disease progresses slowly, it eventually affects one’s ability to walk in a more or less conducive manner.
Who is affected by muscular dystrophy?
In most cases MD appears in infancy, but it’s not uncommon for symptoms to start manifesting in teens or adults.
There are different kinds of muscular dystrophy, the most common and severe form being Duchenne muscular dystrophy (DMD) Caused by a genetic flaw or defect, Duchenne MD is more common in males than females [1} and affects about 1 in every 3,500 boys worldwide.
The onset of Duchenne muscular dystrophy occurs between the ages of 2 and 6, and evolves slowly. Muscles becoming weaker year after year, and the spine and limbs becoming progressively deformed. In most cases, children affected by this form of the disease become wheelchair dependent by the age of 12.
People suffering from Duchenne MD often die in their 20s, and those who survive usually experience some degree of cognitive impairment. The shortening of tendons and muscles limits the mobility of sufferers even more, and breathing and heart problems can occur.
Treatments for Duchenne muscular dystrophy
There is currently no known cure for DMD, but there are treatments that help to reduce some of the symptoms and strengthen the patient’s muscles to some degree. Physiotherapy is commonly used for slowing down the loss of muscle mass and for maintaining flexibility or reducing muscle stiffness. Steroids are also used to slow down muscle wasting, but the severe side effects of steroids often cause more harm than good, such as bone weakening or cardiovascular problems.In a healthy organism, damaged muscles repair themselves thanks to a series of cells that include muscle stem cells, called satellite cells. In Duchene muscular dystrophy, the muscles lack dystrophin, the protein needed for maintaining the integrity of muscle fibers. Without this protein, the burden placed on the body’s naturally occurring muscle stem cells is too intense, rendering the cells unable to repair damaged muscle tissue or to generate new muscle mass to replace wasted mass [6].
For this reason, scar tissue and fat cells take the place of damaged muscle tissue, contributing to muscle weakening and, over time, cause muscles to lose their functional ability. Would it be possible for the damaged muscle fibers to regain their regenerative ability with help from transplanted stem cells?
Research suggests stem cells could be a potential solution for muscle wasting
Different strategies involving stem cells for muscular dystrophy may be on the horizon, research suggests. Scientists have been using stem cells isolated from muscle tissue, bone marrow and blood vessels in lab animals to regenerate muscle fibers that are deficient in dystrophin[3] and results are encouraging.In 2006, researchers managed to restore mobility in two afflicted dogs using stem cells isolated from muscle blood vessels [4], and in 2007 scientists managed to treat Duchenne MD in research mice using a combination of genetic correction and stem cells [3]. The latter study showed that it is possible to correct the genetic error in the cells that no longer produce dystrophin protein, and inject corrected cells stimulating the regeneration of muscles.
Researchers at the Harvard Stem Cell Institute obtained similar results, demonstrating that transplanted muscle stem cells can improve function in mice with MD, while replenishing the stem cell population in muscle fibers [5].
Although it’s still too early to say whether stem cells can cure DMD in humans, it’s clear that there are some promising stem-cell-based approaches for Duchenne MD. One solution is to replace the defective stem cells with healthy stem cells, as these may be able to generate working muscle fibers to replace damaged muscle fibers .
A second solution would be to reduce the inflammation that speeds up the loss and weakening of muscles using certain types of stem cells [2]. Combined treatments, such as mixing stem cell therapies with gene therapies are also being tested and may prove successful in the near future.
References:
- http://www.mayoclinic.org/diseases-conditions/muscular-dystrophy/basics/definition/con-20021240
- http://www.eurostemcell.org/factsheet/muscular-dystrophy-how-could-stem-cells-help
- https://www.mda.org/disease/duchenne-muscular-dystrophy/research
- http://quest.mda.org/article/scientists-bullish-stem-cells-muscle-repair
- http://hsci.harvard.edu/stem-cells-used-treat-muscular-dystrophy-mice
- https://med.stanford.edu/news/all-news/2014/12/stem-cells-faulty-in-duchenne-muscular-dystrophy.html
http://www.mayoclinic.org/diseases-conditions/muscular-dystrophy/basics/definition/con-20021240
- http://www.eurostemcell.org/factsheet/muscular-dystrophy-how-could-stem-cells-help
- https://www.mda.org/disease/duchenne-muscular-dystrophy/research
- http://quest.mda.org/article/scientists-bullish-stem-cells-muscle-repair
- http://hsci.harvard.edu/stem-cells-used-treat-muscular-dystrophy-mice
- https://med.stanford.edu/news/all-news/2014/12/stem-cells-faulty-in-duchenne-muscular-dystrophy.html
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