July 6, 2020

The Niche

Knoepfler lab stem cell blog

Book Excerpt: Stem Cells for Alzheimer’s Disease–Are We There yet?

Test for Alzheimer's DiseaseBelow is an excerpt focused on Alzheimer’s Disease from my new book on stem cells. Stem Cells: An Insider’s Guide, which is targeted to a broad audience of people interested in stem cells.

Alzheimer’s Disease (AD) is one of the most devastating illnesses. It destroys the brain, which shrinks over time (see image from Wikipedia at left) as the disease progresses.

The toll of AD is not only measured in hundreds of billions of dollars in health care costs and millions of deaths, but also in personal and family tragedy that comes with the severe loss of memory that accompanies it in loved ones.

Remarkably, scientists and doctors are getting better at predicting who has pre-clinical AD or who will ultimately get AD before patients are even symptomatic.

I have to wonder, though, would I want to know I will get AD if doctors have no treatment for it? I’m not sure.

At this time nobody really knows what causes AD. There are also no known convincing ways to treat or prevent it either. However, a number of avenues provide hope for the future and stem cells are one of the most interesting.

For example, the New York Times published an article about a relatively new clinical trial being conducted on a Columbian family that has a strong genetic predisposition to AD. Scientists are testing a treatment on this family using an antibody-based drug called Crenezumab. The drug is an antibody that has as its target the distinctive plaques that form in the AD brain even before the disease becomes clinically apparent. Many other drugs are being developed as well, but an overriding challenge is that, as mentioned above, we do not truly understand AD in the same way that we understand other diseases. Thus, further research is essential.

Another possible approach to treat AD is through stem cell-based regenerative medicine therapies. There are three key possible approaches to using stem cells to treat AD:

Regrow brain cells via cell therapy. One avenue is to use stem cells to regenerate or regrow diseased parts of the brain. This approach is what people most commonly think of when they conceive of treating AD with stem cells. The problem with this approach is that the architecture of the brain is physically integral to memory so even if we could grow a fresh, young part of the brain to replace one ravaged by AD, there would be no memories there. It would be like wiping the slate clean. In theory perhaps the person could make new memories going forward in life that could be remembered or they could be re-educated, but this is not what most people imagine as a successful treatment for AD.

Heal with immunomodulation. Another approach is to use stem cells such as MSCs not as rebuilding agents, but rather as healers of the existing brain tissue. In this way of thinking, MSC could heal rather than replace neurons for example. MSCs are akin to the natural doctors of the body. They could have anti-inflammatory and other powers that might ameliorate AD.

Drug delivery. A third concept is using stem cells such as MSCs as drug delivery agents. So for example, instead of giving Crenezumab or some other drug systemically, it is possible that stem cells could directly deliver a drug (e.g. one that targets plaques the way that Crenezumab does) within the brain from cell-to-cell far more effectively than a drug given systemically.

Some of these same kinds of approaches might be applicable to other diseases as well. However, all of them might be stymied to some degree by the potentially harsh or even cytotoxic environment of the AD brain, which may kill transplanted cells before they had a chance to do anything positive.

There are eight clinical trials listed in the national database for Alzheimer’s and stem cells.

Some of these same kinds of approaches might be applicable to other diseases as well.

For more info on using stem cells to treat other diseases here are links to posts in my disease focus series below.

Cancer Stem Cells: a new target

Disease Focus Series: Cancer

Disease Focus Series: HIV/AIDS

Disease Focus Series: Spinal Cord Injury

Disease Focus Series: Osteoarthritis research moving forward

Disease Focus Series: Parkinson’s Disease and promising new pre-clinical results from iPS cells

Disease Focus Series: a big week of exciting progress on Alzheimer’s Disease

Disease Focus Series: Huntington’s Disease, a major new finding