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

Author(s):  
Tanay Dalvi ◽  
Bhaskar Dewangan ◽  
Rudradip Das ◽  
Jyoti Rani ◽  
Suchita Dattatray Shinde ◽  
...  

: 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.

US Neurology ◽  
2017 ◽  
Vol 13 (02) ◽  
pp. 67 ◽  
Author(s):  
Jeffrey Cummings ◽  
Kate Zhong ◽  
Dietmar Cordes ◽  
◽  
◽  
...  

Alzheimer’s disease (AD) is rapidly becoming more common as the global population ages. New treatments are needed and new approaches to drug development are warranted. The phase II challenge for AD treatment development programs is how to provide proof-of-concept (POC) of the candidate agent without a large long trial equivalent to phase III. We propose that the available data support measures of the default mode network (DMN) using functional magnetic resonance imaging (fMRI) as demonstrating the effect of treatment on cognitive circuits critical to human cognition. Improved DMN function with symptomatic cognitive enhancing agents or decreased deterioration of DMN function compared to placebo in trials of disease-modifying agents would support POC and allow progression to phase III with greater confidence.


Author(s):  
Jeffrey Cummings ◽  
Garam Lee ◽  
Aaron Ritter ◽  
Marwan Sabbagh ◽  
Kate Zhong

2020 ◽  
Vol 13 (9) ◽  
pp. 242
Author(s):  
Márcia Martins ◽  
Renata Silva ◽  
Madalena M. M. Pinto ◽  
Emília Sousa

Alzheimer’s disease (AD) is a multifactorial disease characterized by the presence of amyloid plaques, neurofibrillary tangles, and nerve cell death that affects, mainly, older people. After decades of investigation, the search for an efficacious treatment for AD remains and several strategies can be and are being employed in this journey. In this review, four of the most promising strategies, alongside with its most promising agents under investigation or development are highlighted. Marine natural products (MNP) are a source of unique chemical structures with useful biological activities for AD treatment. One of the most promising compounds, a marine-derived acidic oligosaccharide (GV-971) just passed phase III clinical trials with a unique mechanism of action. Combination therapy and multitargeted-directed ligand therapy (MTDL) are also two important strategies, with several examples in clinical trials, based on the belief that the best approach for AD is a therapy capable of modulating multiple target pathways. Drug repurposing, a strategy that requires a smaller investment and is less time consuming, is emerging as a strong contender with a variety of pharmacological agents resurfacing in an attempt to identify a therapeutic candidate capable of modifying the course of this disease.


Author(s):  
Jeffrey Cummings ◽  
Garam Lee ◽  
Kate Zhong ◽  
Jorge Fonseca ◽  
Kazem Taghva

Author(s):  
Jeffrey Cummings ◽  
Garam Lee ◽  
Travis Mortsdorf ◽  
Aaron Ritter ◽  
Kate Zhong

Author(s):  
Jeffrey Cummings ◽  
Garam Lee ◽  
Aaron Ritter ◽  
Marwan Sabbagh ◽  
Kate Zhong

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