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A legislative framework introducing European public health measures on orphan medicinal products came into force in the European Union in April 2000. The aim of the orphan legislation is to stimulate research and development of medicinal products for rare diseases by providing incentives to the sponsors. Incentives include, among others, an unreserved access to the centralized procedure with a 10-year period of market exclusivity and fee reductions including free scientific advice for drug development. Nine years after the implementation of the orphan legislation, more than 690 products have been designated and 58 have received marketing authorizations in Europe. The orphan designations granted to date cover a wide variety of diseases for which there are either no authorized treatments or only limited treatment options with a need for improvement. At the dawn of the tenth anniversary of the orphan legislation, the aim of this article is to review how the European Medicines Agency has supported the mechanisms fostering development of orphan medicines in the E.U. since 2000.

Despite the fact that the threat of a new influenza pandemic has been hovering over us for quite some time, the truth is that the weapons currently licensed for fighting the swine-derived H1N1 virus are not quite up to the current needs. Although considerable effort has been put into developing new vaccines and antivirals, the available agents are basically the same ones as 10 years ago. In this review, we consider novel prophylactic and therapeutic alternatives, which luckily are being proposed by experts in the field. The better understanding and basic knowledge of influenza viruses, including their high variability and potential for antigenic drift, has prompted the development of new antivirals and more efficacious vaccines that hold promise for the near future.

Prostate cancer is the most common noncutaneous malignancy in men and also the third leading cause of death due to cancer in males. The conventional initial therapy for localized advanced or metastatic disease is hormone or androgen deprivation therapy. Although hormone-based therapies generally result in rapid responses, the disease then progresses to a phase when they fail to control the malignancy despite castrate testosterone levels. Some patients with castration-resistant prostate cancer continue to respond to secondary hormonal manipulations, and docetaxel-based chemotherapy improves median survival to about 18 months. Prostate cancer is termed hormone-refractory when it no longer responds to hormonal therapy. Currently, other therapeutic options, such as radical prostatectomy, radiation therapy or cryotherapy offer improvement in survival mostly in early stages. New therapy approaches based on a deeper understanding of especially metastatic prostate cancer are of vital importance. Here we discuss up-to-date clinical trials of agents with novel targets and present paradigms in prostate cancer vaccine therapy, metastasis suppressor genes, and some provocative findings on combination therapies of cytotoxic agents, which might provide a platform for developing effective treatment for advanced prostate cancer.

Immune regulation is one of the most important topics in basic and clinical research, and IL-17-producing T helper cells (Th17) cells and regulatory T-cells (Tregs) are at the forefront of immunological research. The annual World Immune Regulation Meeting gathers some of the best experts in this field, and this year's meeting included presentations on new regulators of Th17 differentiation, novel mechanisms of immunosuppression by Tregs, and innovative systems for the ex vivo generation of Tregs. Novel targets for allergic inflammation were also discussed.

Kisspeptin appears to have a pivotal role in the regulation of reproductive function and may have a therapeutic role in the treatment of disorders of reproduction. In this review we summarise the evidence regarding kisspeptin and its function in the hypothalamic pituitary gonadal axis and also examine future therapeutic applications.

BRCA1/2 mutations are the most commonly identified germ line gene mutations in patients with hereditary breast cancer. These proteins have many critical cellular functions, including repair of DNA double-strand breaks. The role of defective BRCA1/2 as a predictor of response to DNA-damaging agents has been studied extensively in preclinical models, but prospective clinical validation is lacking. Poly [ADP-ribose] polymerase (PARP) inhibitors illustrate the concept of synthetic lethality in cells with defective BRCA1/2 and numerous PARP inhibitors are being evaluated in patients with BRCA1/2-associated tumors. BRCA1/2 mutation or functional loss will likely serve as a useful predictive biomarker of response to treatment with PARP inhibitors.

The Wnt signaling pathway has a role in several cellular processes, including cellular communication, embryonic development and cancer. Recent studies show that the Wnt pathway also has an important role in some aspects of neuronal circuit development, such as neuronal migration, synaptic differentiation, mature synapse modulation and synaptic plasticity. Wnt signaling begins during neural development and is crucial for long-term potentiation in the adult brain. The Wnt pathway may have potential in the prevention of neurodegenerative diseases that involve synaptic impairment. Several years ago our laboratory found a relationship between the loss of Wnt signaling and amyloid-beta-peptide (Abeta) neurotoxicity, which is involved in Alzheimer's disease (AD). The activation of the Wnt signaling cascade prevents Abeta-dependent cytotoxic effects. We proposed that beta-catenin-dependent Wnt ligands have a role in the modulation of presynaptic processes such as neurotransmitter release. beta-catenin-independent Wnt signaling controls the postsynaptic site, increasing the incorporation of PSD-95 and glutamatergic receptors in the postsynaptic region. This could prevent the effects of Abeta exposure at the postsynaptic level. The study of the Wnt pathway is a promising approach in the search for possible targets to fight the deleterious effects of neurodegenerative conditions such as AD.

An international panel of speakers together with approximately 70 delegates were brought together by The Society for Medicines Research's symposium on Optimising Drugs for Local Delivery, held on June 11, 2009 at the Novartis Institutes for Biomedical Research, Horsham, UK. The focus of the conference was on the delivery of drugs direct to the site of action and the consequences of this delivery route on delivery technologies, formulation science and molecular design.