The failure rate for clinical trials to test treatments for neurodegenerative diseases such as Alzheimer’s disease is high. One reason for this high rate of failure may be that potential drugs are derived from research in nonhuman models. The good news is that Harvard stem cell scientist Tracy Young-Pearse and her team have succeeded in producing a method that can enable scientists to study Alzheimer’s in living human cells.
Young-Pearse and her team have successfully converted skins cells from patients with younger onset Alzheimer’s into the types of brain neurons that are affected by the disease. The ability to use neurons made from human cells during research could make it possible to develop therapies more quickly and accurately than in the past.
When it comes to Alzheimer’s, these scientists confirmed what other researchers have observed in mouse models – the fact that the mutations associated with younger onset Alzheimer’s are directly related to protein cleavage errors that cause a rise in amyloid-beta (Aβ) protein 42. Everyone produces this protein, however it’s thought that an error causes it to clump together and form plaques in people with Alzheimer’s disease.
These human derived cells also possess what is considered to be the second hallmark of Alzheimer’s disease. This second hallmark occurs when high amounts of tau protein become distorted enabling the proteins to tangle together.
The relationship between amyloid-beta and tau is an ongoing debate between Alzheimer’s researchers, with some scientists associating amyloid-beta with Alzheimer’s development and others associating tau with the disease. Still other scientists feel that it’s the combination of these factors that causes the symptoms of Alzheimer’s disease.
Younger onset Alzheimer’s disease can occur in people from their 30s onward into their 60s. When the disease strikes younger people genetic mutations are considered to be the cause of the disease. The more common form of Alzheimer’s disease first shows symptoms in people in their late 60s and older. It’s thought that while genes may play some part in this type of Alzheimer’s as well, it has not yet been associated with specific mutations.
Young-Pearse said, “In familial [younger onset] Alzheimer’s, it’s pretty well accepted that a change in amyloid-beta generation sparks something that leads to disease. In the sporadic [older onset] form of the disease, we think the problem isn’t necessarily with the generation of amyloid-beta, but possibly with its clearance.”
Young-Pearse wants to follow her team’s findings by using patient-derived cells to discover why Alzheimer’s patients only show the disease in particular areas of the brain, most often the hippocampus which is an area that is crucial for memory recall. For these experiments and others, the ability to use neurons created from human skin will enable them to determine more about the human brain without having to extrapolate research from mouse models.
Like most clinical research, this ability to work on human neurons is not likely to produce a cure for Alzheimer’s soon enough to help people who have already developed the disease. However, it’s hoped that the work of these Harvard scientists may have closed a gap in research that could speed along the work of others. Since time is of the essence, this is good news.
Caputo, J. (2014, March 4) Alzheimer’s in a dish: Stem cells from patients offer model and drug-discovery platform for early onset form of disease. Harvard.edu. Retrieved from http://news.harvard.edu/gazette/story/2014/03/alzheimers-in-a-dish/?utm_source=twitter&utm_medium=social&utm_campaign=hu-twitter-general
Published On: April 08, 2014