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Issue title: Therapeutic Trials in Alzheimer’s Disease: Where Are We Now?
Guest editors: Paula I. Moreira, Jesus Avila, Daniela Galimberti, Miguel A. Pappolla, Germán Plascencia-Villa, Aaron A. Sorensen, Xiongwei Zhu and George Perry
Article type: Review Article
Authors: Sun, Miao-Kun; * | Alkon, Daniel L.
Affiliations: Synaptogenix, Inc., New York, NY, USA
Correspondence: [*] Correspondence to: Dr. Miao-Kun Sun, Synaptogenix, Inc. 1185 Avenue of the Americas, 3rd Floor, New York, NY 10036, USA. Tel.: +1 240 366 4146; E-mail: msun@synaptogen.com.
Abstract: Neurodegenerative disorders involve progressive dysfunction and loss of synapses and neurons and brain atrophy, slowly declining memories and cognitive skills, throughout a long process. Alzheimer’s disease (AD), the leading neurodegenerative disorder, suffers from a lack of effective therapeutic drugs. Decades of efforts targeting its pathologic hallmarks, amyloid plaques and neurofibrillary tangles, in clinical trials have produced therapeutics with marginal benefits that lack meaningful clinical improvements in cognition. Delivering meaningful clinical therapeutics to treat or prevent neurodegenerative disorders thus remains a great challenge to scientists and clinicians. Emerging evidence, however, suggests that dysfunction of various synaptogenic signaling pathways participates in the neurodegenerative progression, resulting in deterioration of operation/structure of the synaptic networks involved in cognition. These derailed endogenous signaling pathways and disease processes are potential pharmacological targets for the therapies. Therapeutics with meaningful clinical benefit in cognition may depend on the effectiveness of arresting and reversing the neurodegenerative process through these targets. In essence, promoting neuro-regeneration may represent the only option to recover degenerated synapses and neurons. These potential directions in clinical trials for AD therapeutics with meaningful clinical benefit in cognitive function are summarized and discussed.
Keywords: Alzheimer’s disease, brain-derived neurotrophic factor, cognitive therapy, meaningful clinical benefit, neuroinflammation, neuropharmacology, protein kinase Cɛ
DOI: 10.3233/JAD-240479
Journal: Journal of Alzheimer's Disease, vol. 101, no. s1, pp. S263-S274, 2024
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