The Development of Pharmacological Therapies for Alzheimer’s Disease

Lin, Ping; Sun, Junyu; Cheng, Qi; Yang, Yue; Cordato, Dennis; Gao, Jianqun

doi:10.1007/s40120-021-00282-z

Cited by 11 publications

(6 citation statements)

References 114 publications

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“…Drug delivery systems (DDSs) comprise a wide range of NPs, hydrogels, microformulations (microneedles, microparticles, microspheres and microemulsions) and NPs-loaded hydrogel (NLH) systems. Both NPs and microparticles can improve the therapeutic yield of drugs, protecting them from rapid degradation, improving their bioavailability and providing a more valuable release for the proposed site [ 187 , 209 , 210 ].…”

Section: State-of-the-art Pharmaceutical Formulations and Nanomedicin...mentioning

confidence: 99%

Photobiomodulation in Alzheimer’s Disease—A Complementary Method to State-of-the-Art Pharmaceutical Formulations and Nanomedicine?

Ailioaie

Litscher

2023

Pharmaceutics

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Alzheimer’s disease (AD), as a neurodegenerative disorder, usually develops slowly but gradually worsens. It accounts for approximately 70% of dementia cases worldwide, and is recognized by WHO as a public health priority. Being a multifactorial disease, the origins of AD are not satisfactorily understood. Despite huge medical expenditures and attempts to discover new pharmaceuticals or nanomedicines in recent years, there is no cure for AD and not many successful treatments are available. The current review supports introspection on the latest scientific results from the specialized literature regarding the molecular and cellular mechanisms of brain photobiomodulation, as a complementary method with implications in AD. State-of-the-art pharmaceutical formulations, development of new nanoscale materials, bionanoformulations in current applications and perspectives in AD are highlighted. Another goal of this review was to discover and to speed transition to completely new paradigms for the multi-target management of AD, to facilitate brain remodeling through new therapeutic models and high-tech medical applications with light or lasers in the integrative nanomedicine of the future. In conclusion, new insights from this interdisciplinary approach, including the latest results from photobiomodulation (PBM) applied in human clinical trials, combined with the latest nanoscale drug delivery systems to easily overcome protective brain barriers, could open new avenues to rejuvenate our central nervous system, the most fascinating and complex organ. Picosecond transcranial laser stimulation could be successfully used to cross the blood-brain barrier together with the latest nanotechnologies, nanomedicines and drug delivery systems in AD therapy. Original, smart and targeted multifunctional solutions and new nanodrugs may soon be developed to treat AD.

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Section: State-of-the-art Pharmaceutical Formulations and Nanomedicin...mentioning

confidence: 99%

Photobiomodulation in Alzheimer’s Disease—A Complementary Method to State-of-the-Art Pharmaceutical Formulations and Nanomedicine?

Ailioaie

Litscher

2023

Pharmaceutics

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“…A comprehensive discussion of amyloid-directed AD therapeutics is beyond the scope of this paper; however, recent reviews have provided thorough coverage of this topic ( Bullain and Doody, 2020 ; Avgerinos et al, 2021 ; Decourt et al, 2021 ; Jeremic et al, 2021 ; Lin et al, 2021 ; Restifo, 2021 ; Sun et al, 2021 ; Van Bokhoven et al, 2021 ; Xie et al, 2021 ; Yu et al, 2021 ). Jeremic et al (2021) summarized the late-stage clinical failures of eight secretase inhibitors, and they report on the clinical status of eight amyloid-directed monoclonal antibodies.…”

Section: The Current Status Of Amyloid-targeting Experimental Therape...mentioning

confidence: 99%

ACU193: An Immunotherapeutic Poised to Test the Amyloid β Oligomer Hypothesis of Alzheimer’s Disease

et al. 2022

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Alzheimer’s disease (AD) is an age-related neurodegenerative disease that affects 50 million people worldwide, with 10 million new cases occurring each year. The emotional and economic impacts of AD on patients and families are devastating. Approved treatments confer modest improvement in symptoms, and recently one treatment obtained accelerated approval from the United States Food and Drug Administration (FDA) and may have modest disease modifying benefit. Research over the past three decades has established a clear causal linkage between AD and elevated brain levels of amyloid β (Aβ) peptide, and substantial evidence now implicates soluble, non-fibrillar Aβ oligomers (AβOs) as the molecular assemblies directly responsible for AD-associated memory and cognitive failure and accompanying progressive neurodegeneration. The widely recognized linkage of elevated Aβ and AD spawned a comprehensive 20-year therapeutic campaign that focused primarily on two strategies – inhibition of the secretase enzymes responsible for Aβ production and clearance of Aβ peptide or amyloid plaques with Aβ-directed immunotherapeutics. Unfortunately, all clinical trials of secretase inhibitors were unsuccessful. Of the completed phase 3 immunotherapy programs, bapineuzumab (targeting amyloid plaque) and solanezumab (targeting Aβ monomers) were negative, and the crenezumab program (targeting Aβ monomers and to a small extent oligomers) was stopped for futility. Aducanumab (targeting amyloid plaques), which recently received FDA accelerated approval, had one positive and one negative phase 3 trial. More than 25 negative randomized clinical trials (RCTs) have evaluated Aβ-targeting therapeutics, yet none has directly evaluated whether selective blockage of disease-relevant AβOs can stop or reverse AD-associated cognitive decline. Here, we briefly summarize studies that establish the AD therapeutic rationale to target AβOs selectively, and we describe ACU193, the first AβO-selective immunotherapeutic to enter human clinical trials and the first positioned to test the AβO hypothesis of AD.

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“…The pharmacologic therapies for AD are classified into two classes: acetylcholinesterase (AChE) inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists [7]. However, AChE inhibitors and NMDA receptor antagonists have been linked to side effects.…”

Section: Introductionmentioning

confidence: 99%

Drug Delivery Systems as a Strategy to Improve the Efficacy of FDA-Approved Alzheimer’s Drugs

2022

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Alzheimer’s disease (AD) is the most common form of dementia, with a high impact worldwide, accounting for more than 46 million cases. The continuous increase of AD demands the fast development of preventive and curative therapeutic strategies that are truly effective. The drugs approved for AD treatment are classified into acetylcholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists. The therapeutic effectiveness of those drugs is hindered by their restricted access to the brain due to the blood–brain barrier, low bioavailability, and poor pharmacokinetic properties. In addition, the drugs are reported to have undesirable side effects. Several drug delivery systems (DDSs) have been widely exploited to address these issues. DDSs serve as drug carriers, combining the ability to deliver drugs locally and in a targeted manner with the ability to release them in a controlled and sustained manner. As a result, the pharmacological therapeutic effectiveness is raised, while the unwanted side effects induced by the unspecific distribution decrease. This article reviews the recently developed DDSs to increase the efficacy of Food and Drug Administration-approved AD drugs.

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The Development of Pharmacological Therapies for Alzheimer’s Disease

Cited by 11 publications

References 114 publications

Photobiomodulation in Alzheimer’s Disease—A Complementary Method to State-of-the-Art Pharmaceutical Formulations and Nanomedicine?

Photobiomodulation in Alzheimer’s Disease—A Complementary Method to State-of-the-Art Pharmaceutical Formulations and Nanomedicine?

ACU193: An Immunotherapeutic Poised to Test the Amyloid β Oligomer Hypothesis of Alzheimer’s Disease

Drug Delivery Systems as a Strategy to Improve the Efficacy of FDA-Approved Alzheimer’s Drugs

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