Table of contents


Comment: Antimicrobial innovation: combining commitment, creativity and coherence

Jos W. M. van der Meer, Robin Fears, Dame Sally C. Davies & Volker ter Meulen

p709 | doi:10.1038/nrd4448

Urgent action to tackle antimicrobial resistance must take account of all the scientific opportunities available, find new resources to support academia and emphasize the importance of innovation to policy-makers and to the general public.

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News and Analysis

Momentum builds around new antibiotic business models | PDF (1,093 KB)

p711 | doi:10.1038/nrd4455

False dawn for cystic fibrosis disease modifiers? | PDF (695 KB)

p713 | doi:10.1038/nrd4456

News in Brief

Merck wins first PD1 sprint in US | PDF (602 KB)

p715 | doi:10.1038/nrd4458

Reanalyse this | PDF (602 KB)

p715 | doi:10.1038/nrd4460

Biobusiness Briefs

Market watch: Upcoming catalysts in Q4 2014 | PDF (696 KB)

p716 | doi:10.1038/nrd4449

Biobusiness Briefs

Trial watch: Next-generation antimalarial from phenotypic screen shows clinical promise | PDF (743 KB)

p717 | doi:10.1038/nrd4457

An Audience With

Story Landis | PDF (686 KB)

p718 | doi:10.1038/nrd4454

Story Landis, ex-Director of the US National Institute of Neurological Disorders and Stroke, discusses how she has worked to address a crisis of basic research funding at the Institute.

From the analyst's couch

The cystic fibrosis drug market | PDF (646 KB)

p721 | doi:10.1038/nrd4434

Current treatments for cystic fibrosis are largely symptomatic, but the first disease-modifying drug has recently been approved and others are progressing. This article examines the multitude of agents in the clinical pipeline and their potential market impact in the next 5 years.

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Research Highlights

Cancer: Lipid kinase PIP5K1α as a new target in prostate cancer | PDF (639 KB)

p723 | doi:10.1038/nrd4446

Autoimmune disease: Getting to the root of hair loss in alopecia | PDF (684 KB)

p724 | doi:10.1038/nrd4443

Cardiovascular drugs: Engineered apyrase averts clot formation | PDF (647 KB)

p724 | doi:10.1038/nrd4444

Neuromuscular disorders: Beefing up the right splice variant to treat spinal muscular atrophy | PDF (575 KB)

p725 | doi:10.1038/nrd4445

Anticancer therapy: Bacterial treatment for cancer | PDF (603 KB)

p726 | doi:10.1038/nrd4447

In brief

Cancer: Understanding resistance to antiangiogenic agents | PDF (557 KB)

p726 | doi:10.1038/nrd4450

Transplantation: Hydrogel safely delivers immunosuppressant | PDF (557 KB)

p726 | doi:10.1038/nrd4451

Psychiatric disorders: Enzyme inhibitor improves cognitive function | PDF (557 KB)

p726 | doi:10.1038/nrd4452

Drug design: Guidelines for macrocycle drug design | PDF (557 KB)

p726 | doi:10.1038/nrd4453

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Perspectives

Opinion

Caloric restriction mimetics: towards a molecular definition

Frank Madeo, Federico Pietrocola, Tobias Eisenberg & Guido Kroemer

p727 | doi:10.1038/nrd4391

Caloric restriction can promote health and extend the lifespan of model organisms, and diverse classes of compounds that mimic the biochemical and functional effects of caloric restriction have attracted considerable interest as potential pharmacotherapies for diseases such as diabetes and obesity. Kroemer, Madeo and colleagues propose a unifying definition of caloric restriction mimetics as agents that induce autophagy by promoting protein deacetylation, which could have implications for their development as drugs.

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Reviews

Strategies to improve drug development for sepsis

Mitchell P. Fink & H. Shaw Warren

p741 | doi:10.1038/nrd4368

Sepsis is a potentially fatal systemic disease that is caused by microbial infection. Despite numerous clinical trials, no specific therapeutic agent has yet been approved for this indication. Here, Fink and Warren consider potential reasons for such failures and suggest possible strategies to overcome ongoing challenges, such as improving clinical trial design.

mRNA-based therapeutics — developing a new class of drugs

Ugur Sahin, Katalin Karikó & Özlem Türeci

p759 | doi:10.1038/nrd4278

The therapeutic potential of in vitro-transcribed mRNA (IVT mRNA) extends from prophylactic and therapeutic vaccines to applications such as protein replacement and genome engineering. In this Review, the authors describe the recent developments in the IVT mRNA field, discuss the class-specific challenges with regards to translating IVT mRNA into a biopharmaceutical, and provide an overview of IVT mRNA drugs in development for different indications.