Thursday, April 24, 2014

SciBX: Science-Business eXchange Contents: April 24 2014, Volume 7 / Issue 16

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SciBX: Science-Business eXchange

TABLE OF CONTENTS

April 24 2014, Volume 7 / Issue 16

Analysis

Cover Story
Targets and Mechanisms

The Distillery: Therapeutics

Cancer
Cardiovascular disease
Endocrine/metabolic disease
Inflammation
Musculoskeletal disease
Neurology

The Distillery: Techniques

Assays and screens
Disease models
Drug platforms
Markers
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Analysis

Cover Story

Top

CRISPR in the liver
Amy Donner
doi:10.1038/scibx.2014.447
Although the therapeutic utility of CRISPR-based approaches has yet to be demonstrated, venture dollars are flowing into new companies developing the platform. Proof of concept may come faster than expected as new findings show that a CRISPR-based therapeutic can correct a mutation in adult mice with genetic liver disease.
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Targets and Mechanisms

Top

Reversing (heart) failure in Friedreich's ataxia
Michael J. Haas
doi:10.1038/scibx.2014.448
Heart failure accounts for over half the deaths in patients with Friedreich's ataxia, but there are no therapies for the neurodegenerative disease. Now, a team of French researchers has shown that i.v. frataxin gene therapy could prevent or reverse heart failure in a mouse model of the disease.
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Leveling cancer through IL-15
Kai-Jye Lou
doi:10.1038/scibx.2014.449
Findings that link high IL-15 levels in tumors with increased local T cell proliferation and favorable patient outcomes position the cytokine as a robust prognostic and complement ongoing efforts to develop IL-15 as a therapeutic in colorectal cancer and other malignancies.
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Mired in miR-25
Lauren Martz
doi:10.1038/scibx.2014.450
New evidence that miR-25 inhibition can help treat heart failure contradicts earlier results. Although the current study shows that blocking miR-25 restores SERCA2A—and thus improves cardiac contractility—discrepancies between the studies need to be resolved before a therapy can be developed.
Full Text | PDF

Distillery: Therapeutics

Cancer

Top

Homeobox C10 (HOXC10)
doi:10.1038/scibx.2014.451
In vitro and mouse studies suggest decreasing HOXC10 methylation could help treat breast cancers resistant to aromatase inhibitors and other estrogen-depleting therapies.
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X-box binding protein 1 (XBP1)
doi:10.1038/scibx.2014.452
Studies in mice and patient samples suggest inhibiting the XBP1 branch of the unfolded protein response could help treat triple-negative breast cancer (TNBC).
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7,8-Dihydro-8-oxoguanine triphosphatase (NUDT1; MTH1)
doi:10.1038/scibx.2014.453
In vitro, cell culture and mouse studies have identified inhibitors of MTH1 that could help treat cancer.
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CD248 endosialin (TEM1)
doi:10.1038/scibx.2014.454
Mouse studies suggest a DNA plasmid encoding a TEM1–tetanus toxoid (TT) fusion peptide could be used as a cancer vaccine.
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G protein–coupled receptor 39 (GPR39); smoothened (SMO)
doi:10.1038/scibx.2014.455
In vitro studies suggest agonizing GPR39 could inhibit the hedgehog pathway to help treat cancer.
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IL-15
doi:10.1038/scibx.2014.456
Patient studies suggest IL-15 could be useful for treating colorectal cancer.
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PTK7 protein tyrosine kinase 7 (PTK7; CCK4)
doi:10.1038/scibx.2014.457
Studies in mice and patient samples suggest inhibiting PTK7 could be useful for treating lung adenocarcinomas.
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Glycogen dependent kinase 3 (GSK3)
doi:10.1038/scibx.2014.458
Zebrafish and cell culture studies suggest GSK3 inhibition could help treat embryonal rhabdomyosarcoma (ERMS).
Full Text | PDF

Cardiovascular disease

Top

Adenosine A1 receptor (ADORA1)
doi:10.1038/scibx.2014.459
In vitro studies identified a biased ADORA1 agonist that could help treat cardiovascular diseases without common side effects.
Full Text | PDF

Endocrine/metabolic disease

Top

Dipeptidyl peptidase-4 (DPP-4; CD26)
doi:10.1038/scibx.2014.460
Mouse studies suggest a DPP-4 peptide vaccine could help treat type 2 diabetes.
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Glucosidase-β bile acid 2 (GBA2)
doi:10.1038/scibx.2014.461
Mouse studies suggest inhibiting GBA2 could help treat type 1 Gaucher's disease.
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Iroquois homeobox 3 (IRX3)
doi:10.1038/scibx.2014.462
In vitro and mouse studies suggest decreasing IRX3 expression could help treat obesity.
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Ubiquitin D (UBD; FAT10)
doi:10.1038/scibx.2014.463
Mouse studies suggest inhibiting FAT10 could help treat obesity.
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Inflammation

Top

Nav1.6 (PN4; SCN8A)
doi:10.1038/scibx.2014.464
In vitro and mouse studies identified a Nav1.6 inhibitor that could help treat optic neuritis, which is often an initial sign of multiple sclerosis (MS).
Full Text | PDF

Musculoskeletal disease

Top

Hypoxia-inducible factor 1α (HIF1A; HIF1α); notch 1 (NOTCH1)
doi:10.1038/scibx.2014.465
Mouse studies suggest stimulating expansion of a vascular endothelial vessel subtype in bone could help treat fractures or age-dependent osteoporosis.
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Neurology

Top

Frataxin (FXN; FRDA)
doi:10.1038/scibx.2014.466
Mouse studies suggest FXN gene therapy could help prevent or treat heart failure in patients with Friedreich's ataxia.
Full Text | PDF

Cystathionase (CTH)
doi:10.1038/scibx.2014.467
Studies in mice and human samples suggest dietary supplementation with cysteine could help prevent neurotoxicity in patients with HD.
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MicroRNA let-7b (MIRLET7B; LET-7B); toll-like receptor 7 (TLR7); transient receptor potential A1 (TrpA1)
doi:10.1038/scibx.2014.468
Cell culture and mouse studies suggest inhibiting extracellular MIRLET7B could help treat pain.
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Distillery: Techniques

Assays and screens

Top

Detection of Plasmodium falciparum or Trypanosome infection with ultrasound-based separation of red blood cells (RBCs)
doi:10.1038/scibx.2014.469
An ultrasound-based separation technique could help detect low levels of parasitemia.
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Ex vivo model of HIV latency to screen latency-reversing agents
doi:10.1038/scibx.2014.470
An ex vivo model of latent HIV in patient T cells could help predict clinical efficacy of latency-reversing agents.
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Four-gene recombination proficiency score to guide the use of DNA-damaging cancer therapies
doi:10.1038/scibx.2014.471
Studies in patient tumor samples have identified a four-gene expression signature that could help determine prognosis and guide treatment for various cancers.
Full Text | PDF

Disease models

Top

Humanized mice to model chronic HBV infection
doi:10.1038/scibx.2014.472
Mice with humanized immune and liver cells could be used to model chronic HBV infection.
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Drug platforms

Top

Mice with directed integration of human immunoglobulin transgenes to produce chimeric antibodies with fully human variable domains
doi:10.1038/scibx.2014.473
Transgenic mice that produce chimeric antibodies with fully human variable domains could be used to discover therapeutic antibodies.
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Markers

Top

Blood-based DNA methylation signature for progressive supranuclear palsy (PSP) and frontotemporal dementia (FTD)
doi:10.1038/scibx.2014.474
Studies in human samples have identified a blood-based methylation signature that could be useful for diagnosing PSP and FTD.
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Loss-of-function SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily a member 4 (SMARCA4; BRG1) mutations associated with small-cell carcinoma of the ovary, hypercalcemia type (SCCOHT)
doi:10.1038/scibx.2014.475
Genetic studies suggest loss-of-function mutations in SMARCA4 could help diagnose SCCOHT.
Full Text | PDF

Top

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