Drug Discovery Today: Disease Models Drug Discovery Today: Disease Models RSS feedThis is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Cancer gene therapy: innovations in therapeutic delivery of CRISPR-Cas9
Publication date: Available online 30 May 2017 Source:Drug Discovery Today: Disease Models Author(s): Nicole Lindsay-Mosher, Cathy Su Gene therapy has great potential for use in safe and effective cancer treatments, as it can target oncogenic pathways at a molecular level. The recent development of a genome editing system using clustered regularly interspersed palindromic repeats (CRISPR) has made gene therapy for human diseases much more feasible. To realize the full potential of CRISPR and CRISPR-associated systems (Cas) for cancer treatment, however, this gene editing system must be efficiently and safely delivered ...
Source: Drug Discovery Today: Disease Models - May 31, 2017 Category: Drugs & Pharmacology Source Type: research

Systems pharmacology of hepatic metabolism in zebrafish larvae
Publication date: Available online 26 May 2017 Source:Drug Discovery Today: Disease Models Author(s): Rob C. van Wijk, Elke H.J. Krekels, Thomas Hankemeier, Herman P. Spaink, Piet H. van der Graaf Interspecies translation of pharmacological processes needs to improve to reduce attrition in drug development. Systems pharmacology integrates systems biology and pharmacometrics to characterise and quantify system-specific behaviour upon exposure to drugs in different species. The zebrafish is a suitable vertebrate model organism for systems pharmacology, combining high-throughput potential with high genetic homology to ...
Source: Drug Discovery Today: Disease Models - May 26, 2017 Category: Drugs & Pharmacology Source Type: research

Computational Drug Networks: a computational approach to elucidate drug mode of action and to facilitate drug repositioning for neurodegenerative diseases
Publication date: Available online 18 May 2017 Source:Drug Discovery Today: Disease Models Author(s): Francesco Sirci, Francesco Napolitano, Diego di Bernardo While computational approaches based on chemical structures have been extensively used in drug discovery, drug induced transcriptional responses provide a complementary view of their effects. Network visualizations facilitate the exploration of the chemical space in a comprehensive, integrated view. Systematic approaches can be particularly useful for repositioning drugs acting on the CNS, where polypharmacology, targets promiscuity and pharmacokinetic propertie...
Source: Drug Discovery Today: Disease Models - May 19, 2017 Category: Drugs & Pharmacology Source Type: research

Computational modeling to advance deep brain stimulation for the treatment of Parkinson ’s disease
We describe two classes of models: (1) abstract models, which aim to replicate behaviors without simulating exact patient measures, and (2) clinically predictive models, which aim to simulate patient specific parameters. Abstract models can be used to develop novel patterns of stimulation while clinically predictive models can be used to aid clinicians in selecting therapeutic stimulation parameters for each patient. These principles can likely be applied to stimulation therapies for a number of disorders. (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - May 18, 2017 Category: Drugs & Pharmacology Source Type: research

Innovative in vitro models for breast cancer drug discovery
Publication date: Available online 18 March 2017 Source:Drug Discovery Today: Disease Models Author(s): Elke Kaemmerer, Tayner E. Rodriguez Garzon, Aaron M. Lock, Carrie J. Lovitt, Vicky M. Avery Breast cancer is a complex group of diseases and is one of the most common cancers diagnosed worldwide. Many studies have shown that tumour progression and drug responses vary due to tumour heterogeneity caused by genetic mutations and aberrant protein expression and are also directly affected by the local tumour microenvironment. To identify new targets, and/or evaluate potential new chemotherapeutics, with the ultimate go...
Source: Drug Discovery Today: Disease Models - May 18, 2017 Category: Drugs & Pharmacology Source Type: research

Modeling neurological disease processes using process algebra
Publication date: Available online 18 March 2017 Source:Drug Discovery Today: Disease Models Author(s): Thomas J. Anastasio The sheer complexity of pathogenic neurological processes poses a barrier to understanding that impedes the discovery of more effective drugs or drug combinations for the treatment of neurological disorders. Going forward, the principle means of confronting neurological complexity will be computational modeling, and the effort should employ every available tool. Process algebra is a powerful tool developed in computer science for the purpose of analyzing complicated systems. Its recent appearance i...
Source: Drug Discovery Today: Disease Models - May 18, 2017 Category: Drugs & Pharmacology Source Type: research

Capturing intracellular Ca2+ dynamics in computational models of neurodegenerative diseases
Publication date: Available online 18 March 2017 Source:Drug Discovery Today: Disease Models Author(s): Haroon Anwar Many signaling pathways crucial for homeostatic regulation, synaptic plasticity, apoptosis and immune response depend on Ca2+. Ca2+ dysregulation disrupts normal function of neurons and neuronal networks. This causes severe motor and cognitive disabilities. Understanding how Ca2+ dysregulation triggers disease onset and progression, and affects downstream processes, can help identify targets for treatments. Because of intermingling of molecular pathways, dissecting the role of individual mechanisms and es...
Source: Drug Discovery Today: Disease Models - May 18, 2017 Category: Drugs & Pharmacology Source Type: research

Computer modeling for pharmacological treatments for dystonia
Publication date: Available online 31 March 2017 Source:Drug Discovery Today: Disease Models Author(s): Samuel A. Neymotin, Salvador Dura-Bernal, Herman Moreno, William W. Lytton Dystonia is a movement disorder that produces involuntary muscle contractions. Current pharmacological treatments are of limited efficacy. Dystonia, like epilepsy is a disorder involving excessive activity of motor areas including motor cortex and several causal gene mutations have been identified. In order to evaluate potential novel agents for multitarget therapy for dystonia, we have developed a computer model of cortex that includes some...
Source: Drug Discovery Today: Disease Models - May 18, 2017 Category: Drugs & Pharmacology Source Type: research

Towards knowledge-driven cross-species extrapolation
Publication date: Available online 6 April 2017 Source:Drug Discovery Today: Disease Models Author(s): Christoph Thiel, Ute Hofmann, Ahmed Ghallab, Rolf Gebhardt, Jan G. Hengstler, Lars Kuepfer The transition from preclinical research to clinical phases is a crucial step in pharmaceutical development. In phase I, a new molecular entity is for the first administered to humans, after year-long development in in vitro and in preclinical animal models. However, a significant number of projects is closed during such first-in-man trials, mostly due to reasons of toxicity. This requires for new approaches in pharmaceutica...
Source: Drug Discovery Today: Disease Models - May 18, 2017 Category: Drugs & Pharmacology Source Type: research

Modeling cytokine regulatory network dynamics driving neuroinflammation in central nervous system disorders
Publication date: Available online 10 April 2017 Source:Drug Discovery Today: Disease Models Author(s): Warren D. Anderson, Rajanikanth Vadigepalli A central goal of pharmacological efforts to treat central nervous system (CNS) diseases is to develop systemic therapeutics. This requires a fundamental understanding of CNS function within the organismal context. The immune system constitutes a key link between the periphery and CNS, and many neurological disorders and neurodegenerative diseases are characterized by immune dysfunction. We review the salient opportunities for applying computational models to CNS disease re...
Source: Drug Discovery Today: Disease Models - May 18, 2017 Category: Drugs & Pharmacology Source Type: research

Reverse engineering the inflammatory “clock”: from computational modeling to rational resetting
Publication date: Available online 15 April 2017 Source:Drug Discovery Today: Disease Models Author(s): Yoram Vodovotz Properly-regulated inflammation is central to homeostasis, and becomes dysregulated after traumatic injury, hemorrhage, and sepsis. Inflammation is a dynamic, complex system whose function, like that of an analog clock, cannot be discerned simply from a laundry list of its parts (data). Dynamic approaches to data-driven computational modeling can be thought of as the “gears” and “hands” of the “clock,” and have led to insights regarding principal drivers, dynamic networks, feedbacks, and reg...
Source: Drug Discovery Today: Disease Models - May 18, 2017 Category: Drugs & Pharmacology Source Type: research

Development of quantitative systems pharmacology and toxicology models within consortia: experiences and lessons learned through DILIsym development
This article highlights lessons learned from past experiences associated with The DILI-sim Initiative – a collaborative effort focused on developing DILIsym software for predicting drug-induced liver injury (DILI). (Source: Drug Discovery Today: Disease Models)
Source: Drug Discovery Today: Disease Models - May 18, 2017 Category: Drugs & Pharmacology Source Type: research

Preclinical models of childhood cancer for the development of targeted therapies
Publication date: Available online 3 March 2017 Source:Drug Discovery Today: Disease Models Author(s): Raushan T. Kurmasheva, Peter J. Houghton Childhood cancer represents a diverse group of malignancies that overall constitute approximately one percent of human cancer. With current multimodality therapies comprising surgery, radiation therapy and intensive chemotherapy, about seventy percent of children are cured of disease, and the 5-year Event-Free survival is approaching 80%. However, gains from current cytotoxic therapies come with a severe cost to the health of survivors. These rare cancers present unique challen...
Source: Drug Discovery Today: Disease Models - March 2, 2017 Category: Drugs & Pharmacology Source Type: research

The use of dynamic computational models of neural circuitry to streamline new drug development
Publication date: Available online 1 March 2017 Source:Drug Discovery Today: Disease Models Author(s): Jeffrey E. Arle, Kristen W. Carlson We propose a relatively novel use of dynamic models of neural circuitry in the process of new drug development for neurological disorders. A neural circuit model of depressive disorder was developed. Differences in synaptic activation represented variations in drug binding affinity strength for ten putative molecules. Circuit dynamics led to changes in firing rates compared to normal and depressed baselines. Differing abilities to affect circuitry dynamics not linearly related to bi...
Source: Drug Discovery Today: Disease Models - February 28, 2017 Category: Drugs & Pharmacology Source Type: research

Computer modeling of ischemic stroke
Publication date: Available online 21 February 2017 Source:Drug Discovery Today: Disease Models Author(s): Adam J.H. Newton, William W. Lytton The occlusion of a blood vessel in the brain causes an ischemic stroke. Current treatment relies on restoration of blood flow within 3hours. Substantial research has focused on neuroprotection to spare compromised neural tissue and extend the treatment time window. Despite success with animal models and extensive associated clinical testing, there are still no therapies of this kind. Ischemic stroke is fundamentally a multiscale phenomenon where a cascade of changes triggered by...
Source: Drug Discovery Today: Disease Models - February 20, 2017 Category: Drugs & Pharmacology Source Type: research