Articles in 2012

In recent years, the pharmaceutical industry has struggled to deliver new therapies, especially for diseases that affect the most vulnerable in developing countries. The global health community can fill this vacuum by catalyzing innovative partnerships across academia, government and the private sector, fostering a more rigorous environment for scientific decision making and creating the tools and infrastructure to conduct effective translational research.

Hydrocephalus describes an expansion of the cerebral ventricles that is associated with decreased cerebral volume and compromised neurological function. Although hydrocephalus mostly occurs sporadically, it is frequently associated with diseases caused by defective cilia function, including Bardet–Biedl syndrome (BBS). A new study reveals that hydrocephalus in a mouse model of BBS is related to defective proliferation and apoptosis of neural progenitor cells (NPCs) and can be rescued with lithium treatment (pages 1797–1804).

In neuroinflammatory diseases such as multiple sclerosis, ion channels may fan the embers of neurodegeneration. A new study shows that the cation channel TRPM4 (transient receptor potential melastatin 4) crucially contributes to axonal loss in an animal model of multiple sclerosis (pages 1805–1811).

Another year, another round of approvals, mixed reviews and high-profile failures. We look back on which medicines made the headlines.

This year has proven to be a veritable cliff-hanger for the world of biomedicine. At the same time that the US government stands poised on the brink of the so-called 'fiscal cliff', pharmaceutical companies are stumbling with the industry's 'patent cliff' and academic researchers face the looming 'funding cliff'. But not everything in 2012 was so dire, with dozens of new drugs to hit worldwide markets and countless discoveries made to enable the next generation of medicines. What follows are a set of 'Cliff's notes' to the year that was for the field.

From the microbiome to the microenvironment, certain areas of biomedicine saw fast-paced discovery this year. Here's a rundown of the papers that helped these fields advance quickly in 2012.

In spite of years of effort, we still lack highly efficacious vaccines against HIV, tuberculosis, malaria and numerous other widespread pathogens. Two recent setbacks in vaccine trials suggest that it's time to rethink how new vaccines are developed and to investigate what can be learned from the existing armament of childhood vaccines.

There is a growing appreciation of the importance of circadian regulation in energy homeostasis, and the dysregulation of the circadian clock has been associated with obesity and metabolic abnormalities. A new study shows that adipocyte-specific deletion of a core circadian clock gene, Arntl (Bmal1), in mice shifts the timing of their feeding behavior, resulting in obesity (pages 1768–1777).

Despite the irrefutable role of inflammation in psoriasis, a complete knowledge of what immune cells and cytokines are involved during initiation and progression of this skin disease is lacking. Moreover, the complexities of the immune cell network and potential differences between mice and humans have led to translational failures. It is therefore important that we acquire in-depth understanding of what inflammatory players, of the many involved, are crucial, if we wish to develop effective therapies. In 'Bedside to Bench', James Krueger discusses how a subset of T cells, T_H17 cells, which release interleukin-17 in humans, seem to be essential for pathogenesis of psoriasis. The interplay between interleukin-17 and other cytokines that may potentially be involved in psoriasis also needs further investigation. Additionally, there are open questions as to what subset of T cells, other than T_H17, also produce interleukin-17 and when. In 'Bench to Bedside', Burkhard Becher and Stanislav Pantelyushin examine this issue by looking at a mouse model of skin inflammation that resembles psoriasis in humans. A class of skin-invading innate immune cells called γδ T cells was shown to drive skin inflammation in this model, particularly during the early stages of the disease, suggesting that innate immunity plays an important part in the initiation of psoriasis.

Many mechanisms can contribute to complex diseases such as metabolic diseases; thus, combination therapies may be required to target individual underlying pathological mechanisms. A new study combines glucagon-like peptide-1 (GLP1) and estrogen in a single molecule, allowing selective targeting of this conjugate to cells that express the GLP1 receptor. This strategy improves the metabolic profile of obese mice without the adverse side effects associated with estrogen therapy (pages 1847–1856).

Delayed blood count recovery is a major cause of morbidity and mortality in people undergoing stem cell transplantation or intensive chemotherapy. Treatment with hematopoietic growth factors can accelerate hematopoiesis, but prolonged cytopenias still occur. A new study shows that inhibition of dipeptidylpeptidase IV augments the activity of certain hematopoietic growth factors, providing a new approach to potentially treat cytopenias (pages 1786–1796).