Drug repositioning for Alzheimer's disease

Corbett, Anne; Pickett, James; Burns, Alistair; Corcoran, Jonathan; Dunnett, Stephen B.; Edison, Paul; Hagan, Jim J.; Holmes, Clive; Jones, Emma; Katona, Cornelius; Kearns, Ian; Kehoe, Patrick Gavin; Mudher, Amritpal; Passmore, Anthony Peter; Shepherd, Nicola; Walsh, Frank L.; Ballard, Clive

doi:10.1038/nrd3869

Cited by 249 publications

(230 citation statements)

References 147 publications

(33 reference statements)

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“…Several major diseases are known to contribute to the risk of developing AD, such as hypertension and diabetes. Accordingly, some of the approved therapeutics for these disease conditions, especially those known to penetrate the blood-brain barrier (BBB), have been actively investigated to evaluate their potential as AD drugs [12,13]. Drug repositioning projects are often supported by various experimental data such as preclinical efficacy of select drugs in models of AD.…”

Section: Drug Repositioning For Ad Applicationmentioning

confidence: 99%

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Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

Kim

2015

Neurotherapeutics

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Summary Alzheimer's disease (AD) is the most common cause of dementia and represents one of the highest unmet needs in medicine today. Drug development efforts for AD have been encumbered by largely unsuccessful clinical trials in the last decade. Drug repositioning, a process of discovering a new therapeutic use for existing drugs or drug candidates, is an attractive and timely drug development strategy especially for AD. Compared with traditional de novo drug development, time and cost are reduced as the safety and pharmacokinetic properties of most repositioning candidates have already been determined. A majority of drug repositioning efforts for AD have been based on positive clinical or epidemiological observations or in vivo efficacy found in mouse models of AD. More systematic, multidisciplinary approaches will further facilitate drug repositioning for AD. Some experimental approaches include unbiased phenotypic screening using the library of available drug collections in physiologically relevant model systems (e.g. stem cell-derived neurons or glial cells), computational prediction and selection approaches that leverage the accumulating data resulting from RNA expression profiles, and genome-wide association studies. This review will summarize several notable strategies and representative examples of drug repositioning for AD.

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Section: Drug Repositioning For Ad Applicationmentioning

confidence: 99%

“…The drug repositioning approach can also substantially reduce the risk associated with conventional drug discovery by using existing pharmacokinetic, toxicology and safety data. For AD, drug repositioning is a very attractive strategy that should be more actively pursued [11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Drug Repositioning Approaches for the Discovery of New Therapeutics for Alzheimer's Disease

Kim

2015

Neurotherapeutics

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“…62,63 This allowed researchers to search drugs already known and used for other pathologies and in which the clinical phase I and phase II were already completed, reducing the risk of investment for sponsors in case the clinical study result failed.…”

Section: Analogs Of Oxac: Repositioning Of Drugs Against Glutamate Tomentioning

confidence: 99%

A novel mechanism of neuroprotection: Blood glutamate grabber

Castillo

Loza

Mirelman

et al. 2015

J Cereb Blood Flow Metab

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Glutamate excitotoxicity is a primary contributor of ischemic neuronal death and other cellular components of the neurovascular unit. Several strategies have been developed against glutamate excitotoxicity, however none of them have not shown positive results in the clinical practice so far. Nowadays, the concept of blood/brain glutamate grabbing or scavenging is well recognized as a novel and attractive protective strategy to reduce the excitotoxic effect of excess extracellular glutamate that accumulates in the brain following an ischemic stroke. The main advantage of this novel therapeutic strategy is that it occurs in the blood circulation and therefore does not affect the normal brain neurophysiology, as it has been described for other drug treatments used against glutamate excitotoxicity. In this work we report all experimental data from the beginning of our studies, focused on stroke pathology, and we describe new findings about the potential application of this therapy. Future clinical trials will allow to know the real efficacy of this novel therapeutic strategy in stroke patients.

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“…A main barrier to retinoid therapy in AD is tolerability in frail older people due to the side-effect profile of the drugs including impaired liver function, skin exfoliation, headache, myalgia and abnormal lipids. Interestingly however, consultation with people with AD and their carers revealed a willingness to accept a fairly high level of adverse effects [7]. Of particular note and in a very exciting development, clinical trials of candidate drugs within each of the identified classes of candidate drug are now underway or will be commencing within the next six months.…”

mentioning

confidence: 99%

“…A recent systematic review, which utilised an extensive Delphi-style iterative process involving expert and industry representatives, recommended some agents for fast-tracking to clinical trial [7]. These included antihypertensives, antibiotics, anti-diabetic treatments and retinoid therapy.…”

mentioning

confidence: 99%