Induced pluripotent stem cells — opportunities for disease modelling and drug discovery

Grs̆ković, Marica; Javaherian, Ashkan; Strulovici, Berta; Daley, George Q.

doi:10.1038/nrd3577

Cited by 438 publications

(356 citation statements)

References 174 publications

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“…Small molecule screenings for Aβ biogenesis and Aβ toxicity have been described in mouse embryonic stem cellderived pyramidal neurons and commercial human induced pluripotent stem (iPS) cell-derived neurons [33,39]. While human patient-derived stem cells (e.g., iPS cells) carry great promise [40,41], their productive and reliable use for drug screening applications such as HTS remains challenging owing to laborious maintenance, which makes automation impractical [42][43][44]. Furthermore, genetic and epigenetic variability among patients may influence pharmacological responsiveness [45].…”

Section: Phenotypic Approachesmentioning

confidence: 99%

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: Phenotypic Approachesmentioning

confidence: 99%

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

Kim

2015

Neurotherapeutics

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“…In disease modeling studies multipotent stem cells like ES cells or iPS cells give results that include targeted cells, without the contamination of other cells (Mackay-Sim, 2013). Therefore, iPS cells are useful in the modeling of numerous brain diseases because of their ability to be differentiated into specific cells of interest, e.g., sensory neurons (Grskovic et al, 2011;Mackay-Sim, 2012). …”

Section: Olfactory Sensory Neuron Production From Ips Cellsmentioning

confidence: 99%

Pluripotent stem cells and their use in hearing loss

Kepekçi¹,

Özturan²,

Köker³

2016

Turk J Biol

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Throughout its half a century of development, stem cell research has included two main fields: embryonic stem (ES) cell research and the reprogramming of body somatic cells. In the present review we focused on stem cell reprogramming and its relation with otolaryngology. The human body somatic cells are transformed into pluripotent cells by three basic methods: the somatic nuclear transfer method, the somatic cell fusion method (getting cellular pluripotent capacity in cellular reprogramming), and by transcription factors influencing the body somatic cells to generate reprogrammed induced pluripotent stem (iPS) cells. ES cells and iPS cells have pluripotency and differentiate into cells originating from the three germ layers; they are preferred for cellular treatment, drug development, and disease modeling research. Because of ethical restrictions in obtaining ES cells, iPS cells are an alternative pluripotent cell source and patient-specific autologous pluripotent cells are obtained by this method. Cellular treatment and regenerative medicine with pluripotent cells are currently developing and we aimed to raise awareness about this topic in our paper on using iPS cell technology in the biological treatment of hearing loss, which is an important area of research in otolaryngology.

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“…Existing treatments (especially lithium) and the gradual emergence of insights into the neurobiology of the disorder provide potential targets (table 1). Opportunities should increase with the implementation of new methods such as the use of induced pluripotential stem cells to provide in-vitro models of neural systems, 94 the identification of genetic and epigenetic factors, 95,96 and the use of optogenetics to develop more precise animal models. 97 Meanwhile, faced with the neurobiological complexity of the disorder, present approaches to drug discovery and repurposing will need to use existing targets in addition to any novel targets such as oxidative damage.…”

Section: Future Directionsmentioning

confidence: 99%

The Treatment of Bipolar Disorder

Möller¹,

Nasrallah²

2017

Oxford Medicine Online

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We review recent developments in the acute and long-term treatment of bipolar disorder and identify promising future routes to therapeutic innovation. Overall, advances in drug treatment remain quite modest. Antipsychotic drugs are effective in the acute treatment of mania; their efficacy in the treatment of depression is variable with the clearest evidence for quetiapine. Despite their widespread use, considerable uncertainty and controversy remains about the use of antidepressant drugs in the management of depressive episodes. Lithium has the strongest evidence for long-term relapse prevention; the evidence for anticonvulsants such as divalproex and lamotrigine is less robust and there is much uncertainty about the longer term benefits of antipsychotics. Substantial progress has been made in the development and assessment of adjunctive psychosocial interventions. Long-term maintenance and possibly acute stabilisation of depression can be enhanced by the combination of psychosocial treatments with drugs. The development of future treatments should consider both the neurobiological and psychosocial mechanisms underlying the disorder. We should continue to repurpose treatments and to recognise the role of serendipity. We should also investigate optimum combinations of pharmacological and psychotherapeutic treatments at different stages of the illness. Clarification of the mechanisms by which different treatments affect sleep and circadian rhythms and their relation with daily mood fluctuations is likely to help with the treatment selection for individual patients. To be economically viable, existing psychotherapy protocols need to be made briefer and more efficient for improved scalability and sustainability in widespread implementation.

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Induced pluripotent stem cells — opportunities for disease modelling and drug discovery

Cited by 438 publications

References 174 publications

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

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

Pluripotent stem cells and their use in hearing loss

The Treatment of Bipolar Disorder

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