Renewed Hope for Alzheimer’s

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A July 2022 Pharmaceutical Technology® article (1) outlined that new therapeutics and breakthroughs in neurosciences have lagged far behind oncology or infectious diseases. In Alzheimer’s disease, despite knowing for decades that p-tau and amyloid plaques are established hallmarks, current armaments are severely constrained to drugs that ameliorate disease progression in people living with early Alzheimer’s disease, such as Aduhelm and Leqembi, or drugs that tackle memory and cognitive decline, such as Cholinesterase inhibitors such as Aricept, Exelon, and Razadyne, and Glutamate regulators. All have efficacy questions swirling, while some also have considerable side effects issues, including attendant brain swelling problems (2), and therefore, “current therapy using anti-plaque approach might not be the best option to tackle these diseases” (1).

Neurons are comparatively long-lived cells but are destroyed by Alzheimer’s. Today significant progress can be relayed based on the underlying biology of how this happens. Professor Bart De Strooper, group leader at VIB-KU Leuven Center for Brain and Disease Research, contends, “Our study sheds light on the previously murky waters of Alzheimer’s disease, revealing a potential key player in neuronal loss—an RNA gene called MEG3, and the process of necroptosis” (3). This study contrasted mouse neurons to human, which resisted cell death by comparison, which if analyzed and understood, could provide a protective treatment avenue. As the study itself emphasizes, “Down-regulation of MEG3 and inhibition of necroptosis using pharmacological or genetic manipulation of receptor-interacting protein kinase 1 (RIPK1), RIPK3, or mixed lineage kinase domain-like protein (MLKL) rescued neuronal cell loss in xenografted human neurons” (4). Meaning the effects of the disease, including neuronal tangles and necroptosis, was successfully reduced.

It has been a long wait, but for Alzheimer’s at least, this is the beginning of renewed hope.

References

• Necdina, M. What is Wrong with the Neuroscience
  Drug Market? Pharm.Technol. 2022 46 (7).
• Alzheimer’s Association, www.alz.org (accessed Sept. 18, 2023).
• UK Research and Innovation. New Study Discovers How Neurons Die in Alzheimer’s Disease. UK Research and Innovation, www.ukri.org (accessed Sept. 18, 2023).
• Balusu, S.; Horre, K.; Thrupp, N.; et al. MEG3 Activates Necroptosis in Human Neuron Xenografts Modeling Alzheimer’s Disease. Science, 2023 381 (6663) pp.1176-1182.

About the Author

Mike Hennessy Jr. is the President and CEO of MJH Life Sciences.

Article Details

Pharmaceutical Technology

Volume 47, No.10

October 2023

Page 8

Citation

When referring to this article, please cite it as Hennessy, M. Renewed Hope for Alzheimer’s. Pharmaceutical Technology 47 (10) 2023 8.