News & Comment

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.

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.

There is increasing interest in understanding how epilepsy initiates and how to thwart the establishment of the disease. Many questions remain open as to what targets may the best for preventing epilepsy and whether any common triggering pathway exists to treat this complex malady. In 'Bedside to Bench', Rod C. Scott and Gregory Holmes discuss alternative therapies to treat neonatal seizures to prevent chronic cognitive impairment and brain developmental problems, which can lead to epilepsy later in life. Increasing inhibitory signals in the developing brain may be useful in dampening brain hyperexcitability—and enhanced susceptibility for seizures—and blocking epilepsy development in children. In 'Bench to Bedside', Annamaria Vezzani argues how the mTOR pathway may be a potential target for blocking epileptogenesis. The role of mTOR in seizures in early life and progression of established disease raises the possibility that mTOR could be a common mediator involved in epilepsy at different stages of disease initiation and progression. Given the lack of current antiepileptic drugs to prevent seizures in children and to block epileptogenesis, developing new disease-modifying therapies remains a priority.