Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics
-
Drugs that block voltage-gated sodium channels are efficacious in the management of neuropathic pain. Accordingly, this class of ion channels has been a major focus of analgesic research both in academia and in the pharmaceutical/biotechnology industry. In this article, we review the history of the use of sodium channel blockers, describe the current status of sodium channel drug discovery, highlight the challenges and hurdles to attain sodium channel subtype selectivity, and review the potential usefulness of selective sodium channel blockers in neuropathic pain.
-
Classification of neuropathic pain has been based on disease entities, anatomical localization, or histological observations. Over the past decade, there has been an explosion in our understanding of the basic mechanisms of neuropathic pain. The exciting advances in basic science are paralleled by the recognition from clinical investigations that neuropathic pain is not a monolithic entity, but instead presents as a composite of pain and other sensory symptoms. ⋯ First, in clinical proof-of-concept trials the study population can be enriched prospectively on the basis of entry criteria defined a priori. This enrichment with patients who potentially require a specific treatment should increase the likelihood for positive trial outcomes. Second, in clinical practice it becomes possible to establish an individualized therapy--that is, to identify the particular patients who require a specific treatment option.
-
Novel approaches to treatment of malignant glioma, the most frequently occurring primary brain tumor, have included the use of a wide range of oncolytic viral vectors. These vectors, either naturally tumor-selective, or engineered as such, have shown promise in the handful of phase I and phase II clinical trials conducted in recent years. The strategies developed for each of the different viruses currently being studied and the history of their development are summarized here. In addition, the results of clinical trials in patients and their implication for future trials are also discussed.