Biological Networks and Drug Discovery—Where Do We Stand?

Geppert, Tim; Koeppen, Herbert

doi:10.1002/ddr.21207

Cited by 15 publications

(8 citation statements)

References 116 publications

(157 reference statements)

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“…The current reductionist paradigm, where human disease and multimorbidity are viewed and classified as more or less isolated entities, does not account for an advanced and integrative shared component hypothesis [ 17 , 25 – 28 ]. In addition to this, the very high failure rate of drug candidates in the prevailing “one disease, one target, one drug” paradigm seems to support this notion [ 80 , 81 ]. The hurdles of regulation towards the co-development of drugs are still high but slowly accounted for by regulation authorities [ 82 , 83 ].…”

Section: Discussionmentioning

confidence: 99%

Excess Costs of Comorbidities in Chronic Obstructive Pulmonary Disease: A Systematic Review

et al. 2015

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BackgroundChronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Comorbidities are often reported in patients with COPD and may influence the cost of care. Yet, the extent by which comorbidities affect costs remains to be determined.ObjectivesTo review, quantify and evaluate excess costs of comorbidities in COPD.MethodsUsing a systematic review approach, Pubmed and Embase were searched for studies analyzing excess costs of comorbidities in COPD. Resulting studies were evaluated according to study characteristics, comorbidity measurement and cost indicators. Mark-up factors were calculated for respective excess costs. Furthermore, a checklist of quality criteria was applied.ResultsTwelve studies were included. Nine evaluated comorbidity specific costs; three examined index-based results. Pneumonia, cardiovascular disease and diabetes were associated with the highest excess costs. The mark-up factors for respective excess costs ranged between 1.5 and 2.5 in the majority of cases. On average the factors constituted a doubling of respective costs in the comorbid case. The main cost driver, among all studies, was inpatient cost. Indirect costs were not accounted for by the majority of studies. Study heterogeneity was high.ConclusionsThe reviewed studies clearly show that comorbidities are associated with significant excess costs in COPD. The inclusion of comorbid costs and effects in future health economic evaluations of preventive or therapeutic COPD interventions seems highly advisable.

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Section: Discussionmentioning

confidence: 99%

Excess Costs of Comorbidities in Chronic Obstructive Pulmonary Disease: A Systematic Review

et al. 2015

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“…Second, the current approach in drug discovery remains target-centric [Enna and Williams, 2009]), with the goal to optimize compounds with high affinity and selectivity for a specific target [Geppert and Koeppen, 2014]. At present, there are no definite molecular targets/complex networks identified for any of the dimensions of schizophrenia or its subtypes.…”

Section: Future Directionsmentioning

confidence: 99%

Improving Current Treatments for Schizophrenia

Maric

Jovičić

Mihaljević

et al. 2016

Drug Development Research

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Preclinical Research After the identification of the schizophrenia as an illness over a century ago, treatment of affected individuals included unspecific, mostly very robust methods including deep insulin coma and lobectomy/leucotomy. The first relatively specific treatment of schizophrenia started about 60 years ago with the antipsychotic chlorpromazine. All currently approved antipsychotic drugs block dopamine receptors, indicating that manipulation of dopaminergic function is fundamental to a therapeutic response in psychosis. Despite refinements in their mechanism of action, the therapeutic effects of subsequent generations of antipsychotics are insufficient in claiming superiority over the first generation, with the possible exception of clozapine. Dopamine receptor blockade is necessary but not always sufficient for antipsychotic response and improvements have been reported with molecules acting on other receptors (glutamate, glycine, cannabidiol, estrogen), intracellular signaling proteins, or products of identified risk genes. Here, we review the current status of drugs under investigation. In addition, we emphasize that the development of the novel compounds to target the underlying cognitive dysfunction and negative symptom dimension of full blown schizophrenia, or attenuated psychosis syndrome and specific endophenotypes related to the increased risk of psychosis in the general population, alongside efforts to deconstruct the concept of schizophrenia(s), represent the best way to meet patient needs for better therapies and more favorable outcomes. Drug Dev Res 77 : 357-367, 2016. © 2016 Wiley Periodicals, Inc.

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“…There is growing evidence that a network approach is needed for successful development of medications for complicated diseases [ 15 ]. Complicated noncommunicable diseases such as cancer, Alzheimer's disease, mental disorders, and heart diseases are caused by multiple molecular abnormalities.…”

Section: Introductionmentioning

confidence: 99%

A Glimpse to Background and Characteristics of Major Molecular Biological Networks

Altaf-Ul-Amin

Katsuragi

Sato

et al. 2015

BioMed Research International

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Recently, biology has become a data intensive science because of huge data sets produced by high throughput molecular biological experiments in diverse areas including the fields of genomics, transcriptomics, proteomics, and metabolomics. These huge datasets have paved the way for system-level analysis of the processes and subprocesses of the cell. For system-level understanding, initially the elements of a system are connected based on their mutual relations and a network is formed. Among omics researchers, construction and analysis of biological networks have become highly popular. In this review, we briefly discuss both the biological background and topological properties of major types of omics networks to facilitate a comprehensive understanding and to conceptualize the foundation of network biology.

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Biological Networks and Drug Discovery—Where Do We Stand?

Cited by 15 publications

References 116 publications

Excess Costs of Comorbidities in Chronic Obstructive Pulmonary Disease: A Systematic Review

Excess Costs of Comorbidities in Chronic Obstructive Pulmonary Disease: A Systematic Review

Improving Current Treatments for Schizophrenia

A Glimpse to Background and Characteristics of Major Molecular Biological Networks

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