Pharmacogenomics and therapeutic strategies for XXXX .

@entity1 @entity5320 @entity4433 @entity303 @entity75 @entity2204 @entity179 @entity5060 @entity195 @entity717
Recent advances in genomic medicine have contributed to the acceleration of our understanding regarding the pathogenesis of @entity303 , improving diagnostic accuracy with the introduction of novel biomarkers and personalizing therapeutics with the incorporation of pharmacogenetic and pharmacogenomic procedures to drug development and clinical practice. Most @entity179 , including @entity195 ( @entity195 ), share some common features, such as a genomic background in which hundreds of genes might be involved, genome-environment interactions, complex pathogenic pathways, poor therapeutic outcomes and @entity717 . The main aim of a cost-effective treatment is to halt disease progression via modification of the functional cascade involving @entity195 genomics, transcriptomics, proteomics and metabolomics. Unfortunately, the drugs available for the treatment of @entity303 are not cost effective. The pharmacological treatment of @entity303 accounts for 10-20% of direct costs, and fewer than 20% of the @entity1 are moderate responders to conventional drugs, some of which may cause important adverse drug reactions. Future antidementia drugs must address the complex pathogenic niche of the disease from a multifactorial perspective. Pharmacogenetic and pharmacogenomic factors may account for 60-90% of drug variability in drug disposition and pharmacodynamics. In addition to antidementia drugs, @entity1 with @entity195 or with other forms of @entity303 need concomitant medications for the treatment of diverse disorders of the CNS associated with progressive @entity75 . Approximately 60-80% of drugs acting on the CNS are metabolized via enzymes of the CYP gene superfamily, and 10-20% of Caucasians are carriers of defective @entity5320 polymorphic variants that alter the metabolism of many psychotropic agents. Only 26% of the @entity1 are pure extensive metabolizers for the trigenic cluster integrated by allelic variants of the @entity5320 , @entity4433 and @entity5060 in combination. Although many genes have been suggested to be associated with @entity195 , with the exception of @entity2204 , most polymorphic variants of potential risk exhibit a very weak association with @entity195 . @entity2204 /4 carriers exhibit a dramatic biological disadvantage in comparison with other genotypes, and @entity195 @entity1 harboring this homozygous condition are the worst responders to conventional drugs. The incorporation of pharmacogenetic/pharmacogenomic protocols into @entity195 research and clinical practice can foster the optimization of therapeutics by helping to develop cost-effective biopharmaceuticals and improving drug efficacy and safety.
