What if you could give people whose memories have been stolen the ability to remember again? I’m talking about curing a population of more than 5 million Americans living with Alzheimer’s disease (AD) – not a small task. Unfortunately, this number is predicted to more than triple by 2050, and with it so will healthcare costs and other burdens to society. The situation is dire enough that president Barack Obama signed a law last year that increased the amount of money to fund AD research, education, outreach, and caregiver support.
This weekend, a story was picked up in the news that brings hope for AD research. South China Morning Post covered a scientific study that claims it can reverse memory loss in mice with Alzheimer’s using a cell-based therapy. The study was published in Stem Cell Reports in mid October by a group of Chinese scientists.
Although the study is still in its early stages and the results are preliminary, what I like about it is its simplicity and logic. The authors decided to generate a type of nerve cell that is typically lost (or dysfunctional) in the brains of AD patients and some mouse models of AD. It’s called a basal forebrain cholinergic neuron, and it lives in an area near the bottom of our brains that’s responsible for processing certain functions such as learning and attention. The scientists proposed that they would replace these lost nerve cells in AD mice with healthy nerve cells derived from stem cells in hopes of restoring memory function.
How they did it
The authors first devised methods to make these specific nerve cells from both mouse and human embryonic stem cells in a dish. They were successful in making nerve cells that expressed the correct markers for cholinergic neurons and functioned properly, meaning they could send the correct electrical signals to other nerve cells.
The next step was to test the functionality of the nerve cells in mouse models of AD. Instead of transplanting adult nerve cells into the brain (which don’t survive very well), the authors transplanted progenitor cells, which developmentally, are more specialized than stem cells and eventually become adult nerve cells.
Brain section from an Alzheimer’s mouse that received a transplant of progenitor cells (green) into the basal forebrain. (Yue et al., 2015)
When the mouse progenitor cells were transplanted into the basal forebrain of AD mice, most of them survived and matured into adult cholinergic nerve cells that were able to function in tandem with the original mouse nerve cells. When they transplanted human progenitor cells into the same area, a majority of the transplanted human cells did not survive (likely due to the mouse immune system rejecting them), however, the ones that did were able to turn into functioning cholinergic neurons.
Then came the final question, could the mouse and human progenitors improve the memory of these forgetful mice? The scientists compared the memories of AD mice that had received mouse or human cholinergic progenitor cells to AD mice that received no treatment and to healthy normal mice. The groups were put through a memory test where they were trained to find a hidden platform in a circular pool of water. Untreated AD mice had trouble finding the platform and couldn’t remember where it was in subsequent trials. However, the AD mice that received either mouse or human progenitor cell transplants six to eight weeks before were able to find the platform more quickly and remember where it was in multiple trials. This suggested that the transplanted nerve cells improved their ability to learn tasks and recall memories.
The water maze tests a mouse’s ability to learn and recall where the hidden platform is. (Image adapted from Credit2M BioTech)
Hold on: Primates before humans
So it seems from this study that replacing cholinergic nerve cells in the basal forebrain area of the brain is a potential approach to reversing memory loss in Alzheimer’s disease. However, the study’s senior author, Naihe Jing, cautioned everyone to not get ahead of themselves.
Dr. Naihe Jing
Mice are still very different from humans, so the results on mice do not guarantee the same success on human patients. Our next step is to test the method on primates. It will probably be a long time before clinical trials can be carried out on human volunteers.
But he also explained that his group is thoroughly testing the safety of their embryonic stem cell based therapy.
We used human embryonic stem cells because this method will eventually be used on humans. If the human neurons can get a footing and grow in the brain of a mouse, the chance is high the effect will be even better on a human host. The biggest concern of this development is safety. We were afraid that the transplanted cells would mutate to other types of neurons or even cause brain tumours. We have been improving the technology and making close observation of the mice for more than seven years. So far no mutation or cancerous development has been detected.
So while we might not have a cell therapy to treat Alzheimer’s in the near future, we can be comforted by the fact that groups like this one are taking all the precautions to develop safe and effective treatments.
Related Links:
The Stem Cellar 