title: Pharmacogenetics in Neurodegenerative Diseases: Implications for Clinical Trials.
abstract: BACKGROUND
  Pharmacogenetics has become extremely important over the last 20 years for identifying individuals more likely to be responsive to pharmacological interventions. The role of genetic background as a predictor of drug response is a young and mostly unexplored field in neurodegenerative diseases.
  
  
  CONCLUSIONS
  Mendelian mutations in neurodegenerative diseases have been used as models for early diagnosis and intervention. On the other hand, genetic polymorphisms or risk factors for late-onset Alzheimer's disease (AD) or other neurodegenerative diseases, probably influencing drug response, are hardly taken into account in randomized clinical trial (RCT) design. The same is true for genetic variants in cytochrome P450 (CYP), the principal enzymes influencing drug metabolism. A better characterization of individual genetic background may optimize clinical trial design and personal drug response. This chapter describes the state of the art about the impact of genetic factors in RCTs on neurodegenerative disease, with AD, frontotemporal dementia, Parkinson's disease, amyotrophic lateral sclerosis, and Huntington's disease as examples. Furthermore, a brief description of the genetic bases of drug response focusing on neurodegenerative diseases will be conducted.
  
  
  CONCLUSIONS
  The role of pharmacogenetics in RCTs for neurodegenerative diseases is still a young, unexplored, and promising field. Genetic tools allow increased sophistication in patient profiling and treatment optimization. Pharmaceutical companies are aware of the value of collecting genetic data during their RCTs. Pharmacogenetic research is bidirectional with RCTs: efficacy data are correlated with genetic polymorphisms, which in turn define subjects for treatment stratification.
authors.forename: Rosanna
authors.initials: R
authors.lastname: Tortelli
authors.forename: Davide
authors.initials: D
authors.lastname: Seripa
authors.forename: Francesco
authors.initials: F
authors.lastname: Panza
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Solfrizzi
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Logroscino
mesh_terms: D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy* / Q000628:therapy*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010597:Pharmacogenetics; D016032:Randomized Controlled Trials as Topic
chemical_list: D018696:Neuroprotective Agents; D003577:Cytochrome P-450 Enzyme System