scholarly journals ALZHEIMER’S DISEASE DRUG DEVELOPMENT PIPELINE 2020

2020 ◽  
pp. 1-2
Author(s):  
M.N. Sabbagh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Stimulation ◽  
Gamma Secretase ◽  
Treatment Combination ◽  
The Past ◽  
Therapeutic Benefits ◽  
Fda Approval ◽  
Bace Inhibitor ◽  
Development Pipeline

On March 21, 2019, the aducanumab development team conducting the EMERGE and ENGAGE studies announced that the trials had met a pre-specified futility endpoint (1). The consequences of that announcement were far reaching, as many companies that had invested heavily in targeting amyloid were left to consider if targeting amyloid still remained a viable strategy for developing effective Alzheimer’s disease (AD) therapeutics. Following that announcement, the remaining BACE inhibitor trials announced safety concerns or efficacy concerns effectively ending elenbecestat, umibecestat, lanabecestat, atabecestat, and verubecestat as possible treatments for AD (2). Given that gamma secretase inhibitors and modulators had failed in the past, altering or halting production of amyloid appears to no longer offer viable therapeutic benefits moving forward. To further complicate this already troubling situation, the TMS/cognitive stimulation treatment combination (3) has not received FDA approval.

Proteolytic processing of the amyloid-beta protein precursor of Alzheimer's disease

2002 ◽  
Vol 38 ◽  
pp. 37-49 ◽  
Author(s):  
Janelle Nunan ◽  
David H Small
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Amyloid Beta ◽  
Alternative Pathway ◽  
Protein A ◽  
Proteolytic Processing ◽  
Gamma Secretase ◽  
Amyloid Beta Protein ◽  
Protein Precursor ◽  
Amyloid Beta Protein Precursor

The proteolytic processing of the amyloid-beta protein precursor plays a key role in the development of Alzheimer's disease. Cleavage of the amyloid-beta protein precursor may occur via two pathways, both of which involve the action of proteases called secretases. One pathway, involving beta- and gamma-secretase, liberates amyloid-beta protein, a protein associated with the neurodegeneration seen in Alzheimer's disease. The alternative pathway, involving alpha-secretase, precludes amyloid-beta protein formation. In this review, we describe the progress that has been made in identifying the secretases and their potential as therapeutic targets in the treatment or prevention of Alzheimer's disease.

Old Drugs with New Tricks; Paradigm in Drug Development Pipeline for Alzheimer’s Disease

2020 ◽  
Vol 20 ◽  
Author(s):  
Tanay Dalvi ◽  
Bhaskar Dewangan ◽  
Rudradip Das ◽  
Jyoti Rani ◽  
Suchita Dattatray Shinde ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Development ◽  
Molecular Targets ◽  
Drug Repurposing ◽  
Phase Iii ◽  
Complex Nature ◽  
New Drug ◽  
Development Pipeline ◽  
Old Drugs

: The most common reason behind dementia is Alzheimer’s disease (AD) and it is predicted to be the third lifethreatening disease apart from stroke and cancer for the geriatric population. Till now only four drugs are available in the market for symptomatic relief. The complex nature of disease pathophysiology and lack of concrete evidences of molecular targets are the major hurdles for developing new drug to treat AD. The the rate of attrition of many advanced drugs at clinical stages, makes the de novo discovery process very expensive. Alternatively, Drug Repurposing (DR) is an attractive tool to develop drugs for AD in a less tedious and economic way. Therefore, continuous efforts are being made to develop a new drug for AD by repursing old drugs through screening and data mining. For example, the survey in the drug pipeline for Phase III clinical trials (till February 2019) which has 27 candidates, and around half of the number are drugs which have already been approved for other indications. Although in the past the drug repurposing process for AD has been reviewed in the context of disease areas, molecular targets, there is no systematic review of repurposed drugs for AD from the recent drug development pipeline (2019-2020). In this manuscript, we are reviewing the clinical candidates for AD with emphasis on their development history including molecular targets and the relevance of the target for AD.

Nanotechnology Based Delivery Systems of Drugs Currently Used to Treat Alzheimer’s Disease

2020 ◽  
Vol 10 (3) ◽  
pp. 228-247
Author(s):  
Niloufar Choubdar ◽  
Sara Avizheh
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Polymeric Nanoparticles ◽  
Biological Fluids ◽  
Delivery Systems ◽  
Original Research ◽  
Sustained Drug Release ◽  
The Past ◽  
Site Of Action ◽  
Therapeutic Compound

Alzheimer’s Disease (AD) is one of the most common forms of dementia affecting over 46 million people, according to AD International. Over the past few decades, there has been considerable interest in developing nanomedicines. Using nanocarriers, the therapeutic compound could be delivered to the site of action where it gets accumulated. This accumulation, therefore, reduces the required doses for therapy. Alternatively, using nanocarriers decreases the side effects. Nanotechnology has had a great contribution in developing Drug Delivery Systems (DDS). These DDS could function as reservoirs for sustained drug release or control the pharmacokinetics and biodistribution of the drugs. In the current review, we have collected 38 original research articles using nanotechnology as DDS for the clinically used cholinesterase inhibitor drugs donepezil (DPZ), Rivastigmine (Riv), and galantamine (Gal) used for AD treatment from 2002 to 2017 from Scopus and PubMed databases. Regarding DDS used for DPZ, most of the research in recent years dealt with polymeric nanoparticles (NPs) including Poly-D, L-Lactide-Co-Glycolide (PLGA), and chitosans (CHs), then Liposomes (LPs), nanogels, and natural products, respectively. In terms of Riv most of the research performed was focused on polymeric NPs including PLGA, polylactic acid (PLA), Poly-Ε-Caprolactone (PCL), poly-alkyl-cyanoacrylates, CH, gelatin and then LPs. The highest application of NPs in regard to Gal was related to modified LPs and polymeric NPs. Polymeric NPs demonstrate safety, higher stability in biological fluids and against enzymatic metabolism, biocompatibility, bioavailability, and improved encapsulation efficacy. LPs, another major delivery system used, demonstrate biocompatibility, ease of surface modification, and amphiphilic nature.

scholarly journals Virtual Reality-Based Cognitive Stimulation on People with Mild to Moderate Dementia due to Alzheimer’s Disease: A Pilot Randomized Controlled Trial

2021 ◽  
Vol 18 (10) ◽  
pp. 5290
Author(s):  
Jorge Oliveira ◽  
Pedro Gamito ◽  
Teresa Souto ◽  
Rita Conde ◽  
Maria Ferreira ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Randomized Controlled Trial ◽  
Virtual Reality ◽  
Cognitive Function ◽  
Controlled Trial ◽  
Cognitive Stimulation ◽  
Randomized Controlled ◽  
Moderate Dementia ◽  
Pilot Randomized Controlled Trial

The use of ecologically oriented approaches with virtual reality (VR) depicting instrumental activities of daily living (IADL) is a promising approach for interventions on acquired brain injuries. However, the results of such an approach on dementia caused by Alzheimer’s disease (AD) are still lacking. This research reports on a pilot randomized controlled trial that aimed to explore the effect of a cognitive stimulation reproducing several IADL in VR on people with mild-to-moderate dementia caused by AD. Patients were recruited from residential care homes of Santa Casa da Misericórdia da Amadora (SCMA), which is a relevant nonprofit social and healthcare provider in Portugal. This intervention lasted two months, with a total of 10 sessions (two sessions/week). A neuropsychological assessment was carried out at the baseline and follow-up using established neuropsychological instruments for assessing memory, attention, and executive functions. The sample consisted of 17 patients of both genders randomly assigned to the experimental and control groups. The preliminary results suggested an improvement in overall cognitive function in the experimental group, with an effect size corresponding to a large effect in global cognition, which suggests that this approach is effective for neurocognitive stimulation in older adults with dementia, contributing to maintaining cognitive function in AD.

Lifestyle intervention to prevent Alzheimer’s disease

2020 ◽  
Vol 31 (8) ◽  
pp. 817-824 ◽  
Author(s):  
Yi Ko ◽  
Soi Moi Chye
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lifestyle Intervention ◽  
Social Engagement ◽  
Treatment Options ◽  
Cognitive Stimulation ◽  
Systemic Review ◽  
Lifestyle Interventions ◽  
Alternative Approaches ◽  
The Brain

AbstractAlzheimer’s disease (AD) is the most common neurodegenerative disease that leads to significant morbidities in elderly. The major pathological hallmark of AD is beta-amyloid plaques (Aβ) and intracellular neurofibrillary tangles (NFTs) deposition in hippocampus of the brain. These abnormal protein deposition damages neuronal cells resulting in neurodegeneration and cognitive decline. As a result of limited treatment options available for this disease, there is huge economic burden for patients and social health care system. Thus, alternative approaches (lifestyle intervention) to prevent this disease are extremely important. In this systemic review, we summarized epidemiological evidence of lifestyle intervention and the mechanisms involved in delaying and/or preventing AD. Lifestyle interventions include education, social engagement and cognitive stimulation, smoking, exercise, depression and psychological stress, cerebrovascular disease (CVD), hypertension (HTN), dyslipidaemia, diabetes mellitus (DM), obesity and diet. The methods are based on a literature review of available sources found on the research topic in four acknowledged databases: Web of Science, Scopus, Medline and PubMed. Results of the identified original studies revealed that lifestyle interventions have significant effects and our conclusion is that combination of early lifestyle interventions can decrease the risk of developing AD.

scholarly journals Signaling Mechanisms of Selective PPARγ Modulators in Alzheimer’s Disease

PPAR Research ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-20 ◽  
Author(s):  
Manoj Govindarajulu ◽  
Priyanka D. Pinky ◽  
Jenna Bloemer ◽  
Nila Ghanei ◽  
Vishnu Suppiramaniam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Adverse Effects ◽  
Therapeutic Potential ◽  
Protein Accumulation ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Continuous Increase ◽  
Therapeutic Benefits ◽  
The Brain

Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by abnormal protein accumulation, synaptic dysfunction, and cognitive impairment. The continuous increase in the incidence of AD with the aged population and mortality rate indicates the urgent need for establishing novel molecular targets for therapeutic potential. Peroxisome proliferator-activated receptor gamma (PPARγ) agonists such as rosiglitazone and pioglitazone reduce amyloid and tau pathologies, inhibit neuroinflammation, and improve memory impairments in several rodent models and in humans with mild-to-moderate AD. However, these agonists display poor blood brain barrier permeability resulting in inadequate bioavailability in the brain and thus requiring high dosing with chronic time frames. Furthermore, these dosing levels are associated with several adverse effects including increased incidence of weight gain, liver abnormalities, and heart failure. Therefore, there is a need for identifying novel compounds which target PPARγ more selectively in the brain and could provide therapeutic benefits without a high incidence of adverse effects. This review focuses on how PPARγ agonists influence various pathologies in AD with emphasis on development of novel selective PPARγ modulators.

Visual imagery: The past and future as seen by patients with Alzheimer’s disease

2019 ◽  
Vol 68 ◽  
pp. 12-22 ◽  
Author(s):  
Mohamad El Haj ◽  
Ahmed A. Moustafa ◽  
Karim Gallouj ◽  
Frédérique Robin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Visual Imagery ◽  
The Past

scholarly journals Tart Cherry Extract and Omega Fatty Acids Reduce Behavioral Deficits, Gliosis, and Amyloid-Beta Deposition in the 5xFAD Mouse Model of Alzheimer’s Disease

2021 ◽  
Vol 11 (11) ◽  
pp. 1423
Author(s):  
Zackary Bowers ◽  
Panchanan Maiti ◽  
Ali Bourcier ◽  
Jarod Morse ◽  
Kenneth Jenrow ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Fatty Acids ◽  
Mouse Model ◽  
Neuronal Morphology ◽  
Omega Fatty Acids ◽  
Tart Cherry ◽  
Therapeutic Benefits ◽  
Model Of Alzheimer’S Disease ◽  
5Xfad Mice

Combined treatments using polyphenols and omega fatty acids provide several therapeutic benefits for a variety of age-related disorders, including Alzheimer’s disease (AD). Previously, we found a commercial product, Total Body Rhythm (TBR), consisting of tart cherry extract, a potent polyphenol, and omega fatty acids, significantly reduced memory, and neuropathological deficits in the 192 IgG-saporin mouse model of AD. The present study assessed the efficacy of TBR for treating behavioral and neuropathological deficits in the 5xFAD model of AD. Both 6- and 12-month-old 5xFAD mice and age-matched wild-type controls received TBR (60 mg/kg) or the equivalent dose of vehicle (0.5% methylcellulose) via oral administration, every other day for two months. All mice were tested in the open field (OF), novel object recognition (NOR), and the Morris water maze (MWM) tasks. In addition, neuronal morphology, neurodegeneration, Aβ plaque load, and glial activation were assessed. TBR treatment reduced memory deficits in the MWM and NOR tests and lessened anxiety levels in the OF task, mostly in the 6-month-old male mice. TBR also protected against neuron loss, reduced activation of astrocytes and microglia, primarily in 6-month-old mice, and attenuated Aβ deposition. These results suggest that the combination of tart cherry extract and omega fatty acids in TBR can reduce AD-like deficits in 5xFAD mice.

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