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A new open access paper takes a look at the potential of regenerative medicine for the treatment of Alzheimer’s disease [1]. The review covers approaches such as spurring the production of new neurons and transplanting new neurons while taking a look at the disease-modeling approaches and techniques that science is now using to refine approaches to treating Alzheimer’s.

The authors here investigate how induced pluripotent stem cells (iPSCs) are contributing to the growing knowledge in the field by allowing researchers to create increasingly refined models of Alzheimer’s disease. A current problem we have is that animal models do not emulate the disease closely enough to lead to translational therapies that work in humans; this is why so many new medicines that work in mice fail in clinical trials. The review takes a look at the challenges and how science is working to develop better models.

Introduction

Alzheimer’s disease (AD) is a chronic neurodegenerative disorder characterized by progressive cognitive decline. AD affects 5–7% of older adults globally (Prince et al., 2013), and the expected number of affected patients is expected to grow continuously as the population ages in most countries. Currently, however, there is no cure for this condition. The Food and Drug Administration approved and actively marketed drugs for AD, including cholinesterase inhibitors and N-Methyl-D-Aspartate antagonists, whose effects improve daily functions to a certain degree (Rogers and Friedhoff, 1996; Tariot et al., 2004), yet they are not capable of altering disease progression. Tremendous efforts have been made to develop novel therapeutics to potentially reverse disease progression. Among the ongoing clinical trials designed to modify AD, a majority of them are intended to ameliorate Aβ, including β-secretase inhibitors, immunotherapies, and anti-aggregation agents (Cummings et al., 2017). Recently, several pioneering spotlighted trials targeting Aβ have met with dissatisfying results in terms of improved cognitive function (Doody et al., 2013; Salloway et al., 2014). One cannot jump to the conclusion that these negative clinical outcomes refute the prevailing amyloid cascade hypothesis, yet lessons should be learned from these dissatisfying results. Interestingly, successful elimination of amyloid in animal models, which typically overexpress APP or presenilin (PS1, PS2) genes, does not guarantee successful cognitive restoration in human patients. On the one hand, AD is a complex disease involving multiple cell types and cellular processes; therefore, targets other than amyloid should be considered and tested. On the other hand, developing solid models that better mimic disease pathologies in terms of NFTs, neuronal loss, and cellular interactions will undoubtedly benefit drug screening and mechanistic investigations. In this review, we will discuss how current advances in stem cell technology might address these unmet needs.

Conclusion

Creating better models that accurately emulate Alzheimer’s disease is urgently needed if we are to create effective therapies that actually translate to humans. There is a lack of current animal models that fully mimic the same pathological features seen in the human disease; the use of iPSCs has revolutionized and will continue to revolutionize Alzheimer’s disease modeling.

Literature

[1] Fang, Y., Gao, T., Zhang, B., & Pu, J. (2018). Recent Advances: Decoding Alzheimer’s Disease With Stem Cells. Frontiers in aging neuroscience, 10, 77.

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About the author

Steve Hill

Steve serves on the LEAF Board of Directors and is the Editor in Chief, coordinating the daily news articles and social media content of the organization. He is an active journalist in the aging research and biotechnology field and has to date written over 500 articles on the topic as well as attending various medical industry conferences. In 2019 he was listed in the top 100 journalists covering biomedicine and longevity research in the industry report – Top-100 Journalists covering advanced biomedicine and longevity created by the Aging Analytics Agency. His work has been featured in H+ magazine, Psychology Today, Singularity Weblog, Standpoint Magazine, and, Keep me Prime, and New Economy Magazine. Steve has a background in project management and administration which has helped him to build a united team for effective fundraising and content creation, while his additional knowledge of biology and statistical data analysis allows him to carefully assess and coordinate the scientific groups involved in the project. In 2015 he led the Major Mouse Testing Program (MMTP) for the International Longevity Alliance and in 2016 helped the team of the SENS Research Foundation to reach their goal for the OncoSENS campaign for cancer research.
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