Cohen C.J.,Xenon Pharmaceuticals
Current Pharmaceutical Biotechnology | Year: 2011
Voltage-gated sodium channels (NaV) are well validated targets for treating pain based both on human genetics and clinical experience. Consequently, there is an extensive literature on sodium channels for the treatment of pain and a number of excellent and thorough reviews have recently appeared; a selection of these is provided. This review does not attempt to evaluate all aspects of the studies in this area, but rather will focuses on several key issues that are incompletely addressed in prior reviews or that represent very recent additions to the literature. Key questions that arise are: 1) How much channel block is required to observe efficacy against neuropathic or inflammatory pain? 2) How can one improve upon the therapeutic index of previously tested NaV blockers? © 2011 Bentham Science Publishers.
Brunham L.R.,University of British Columbia |
Tietjen I.,Xenon Pharmaceuticals |
Bochem A.E.,University of Amsterdam |
Singaraja R.R.,University of British Columbia |
And 7 more authors.
Clinical Genetics | Year: 2011
The scavenger receptor class B, member 1 (SR-BI), is a key cellular receptor for high-density lipoprotein (HDL) in mice, but its relevance to human physiology has not been well established. Recently a family was reported with a mutation in the gene encoding SR-BI and high HDL cholesterol (HDL-C). Here we report two additional individuals with extremely high HDL-C (greater than the 90th percentile for age and gender) with rare mutations in the gene encoding SR-BI. These mutations segregate with high HDL-C in family members of each proband and are associated with a 37% increase in plasma HDL-C in heterozygous individuals carrying them. Both mutations occur at highly conserved positions in the large extracellular loop region of SR-BI and are predicted to impair the function of the SR-BI protein. Our findings, combined with the prior report of a single mutation in the gene encoding SR-BI, further validate that mutations in SR-BI are a rare but recurring cause of elevated HDL-C in humans. © 2011 John Wiley & Sons A/S.