Alzheimer’s Disease: Advances in Drug Development
Abstract
As of 2018, Alzheimer's disease (AD) is the most common form of neurodegenerative dementia. It contributes to a progressive neuron loss, deterioration of memory, and cognitive impairment. Current therapies may provide a symptomatic benefit, but do not treat the underlying process. Ongoing researches focus on understanding the causal mechanisms and finding neuropathological hallmarks of AD. Therapeutic approaches targeting senile plaques or neurofibrillary tangles have not yet resulted in a significant cognitive improvement. However, recent data according to the analysis of AD clinical trials (clinicaltrials.gov database) show promising results. This literature review aims at summarizing the recent advances and at highlighting the most promising results of the ongoing researches. It compares the merits of small-molecules, antibodies, cell, and gene-based therapies and emphasizes the need for treatment at earlier stages of the disease.
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CNP520 (umibecestat) has been shown to reduce burden of amyloid-beta plaques in preclinical animals and is currently undergoing testing phases.
“Similar to other BACE-1 inhibitors, CNP520 (umibecestat (labeled as 11, Figure 5)) has been shown to reduce the burden of amyloid-beta plaques in preclinical animals; it is presently undergoing testing phases [157,166,167].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [157]
β-secretase inhibitors such as lanabecestat, verubecestat, and atabecestat target Bace-1 to decrease synthesis of amyloid beta.
“In order to decrease the synthesis of amyloid beta, β-secretase inhibitors (BACE inhibitors) such lanabecestat (labeled as 8, Figure 5) [157,161,162], verubecestat (labeled as 9, Figure 5) [157,163,164], and atabecestat (labeled as 10, Figure 5) target the enzyme Bace-1 [157,165].”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [157]
γ-secretase inhibitors such as tarenflurbil, avagacestat, and semagacestat lower amyloid beta synthesis by preventing gamma secretase enzyme from functioning.
“This includes γ-secretase inhibitors, such as tarenflurbil (7, Figure 5) [155,156], avagacestat (labeled as 6, Figure 5) [157,158], and semagacestat (5, Figure 5) [159,160]. Their purpose is to lower the synthesis of amyloid beta by preventing the gamma secretase enzyme from functioning.”
From Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease (2024) · cites this paper as [157]
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BackgroundIntratarget Microdosing for Deep Phenotyping of Multiple Drug Effects in the Live Brain
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“This interaction was identified by Liu et al. [36] as crucial for BACE1 inhibitor recognition [37].”
Different drugs used as therapeutic targets against AD till date
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Pharmacotherapy of Alzheimer's disease: A thorny road to success
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“In the paucity of effective disease-modifying approaches for dementia [10], increasing evidence suggests the positive effects of non-pharmacological interventions, such as exercise, cognitive training, and maintenance of ADL [4, 11, 12].”
Causal Association of Alzheimer’s Disease with Low Back Pain: A Mendelian Randomization Study
Li, Y., Zhao, S., Chen, X., Wang, Z., Liang, X., Liu, Y., & Dong, Y. (2025) · Journal of Pain Research · doi:10.2147/jpr.s535802
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Novak, G., Streffer, J. R., Timmers, M., Henley, D. B., Brashear, H. R., Bogert, J., Russu, A., Janssens, L., Tesseur, I. C., Tritsmans, L., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12308258
- Authors
- Piton, M., Hirtz, C., Desmetz, C., Milhau, J., Lajoix, A. D., Bennys, K., Lehmann, S., & Gabelle, A.
- Affiliations
- Université de Montpellier (FR)
- BioCommunication en CardioMétabolique (BC M), University of Montpellier, Montpellier France
- Corresponding author
- Gabelle, Audrey
- ORCID
- Venue
- Journal of Alzheimer s Disease
- Publisher
- SAGE Publications
- Published
- 2018-08-07
- Volume
- 65
- Issue
- 1
- Pages
- 3-13
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2883022092
- Cited by
- 60
- References
- 32
- Citations by year
- 2025: 3 · 2024: 6 · 2023: 4 · 2022: 7 · 2021: 14 · 2020: 15 · 2019: 9 · 2018: 2
- FWCI
- 1.31
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, drug development
- MeSH terms
- Drug Development, Alzheimer Disease, Humans, Antipsychotic Agents
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