Effect of a ciliary neurotrophic factor polymorphism on schizophrenia symptom improvement in an iloperidone clinical trial.
OBJECTIVE
Presence of the null FS63TER allele of the rs1800169 polymorphism in the gene encoding the ciliary neurotrophic factor (CNTF) may increase the risk of schizophrenia. This study prospectively evaluated the CNTF rs1800169 genotype (G/G vs non-G/G) effects on response to iloperidone.


METHODS
Iloperidone 24 mg/day was evaluated in a study of patients with schizophrenia. Efficacy measurements included Positive and Negative Syndrome Scale total (PANSS-T), Brief Psychiatric Rating Scale (BPRS) and Clinical, Global, Impression (CGI) scores. The step-down primary end point was the difference in PANSS-T scores based on CNTF rs1800169 G/G genotype.


RESULTS
This study genotyped 417 patients (279 iloperidone and 138 placebo) for the rs1800169 polymorphism. Iloperidone significantly improved PANSS-T, PANSS positive subscale (PANSS-P), PANSS negative subscale (PANSS-N), BPRS, Clinical Global Impression of Change (CGI-C) and Clinical Global Impression of Severity (CGI-S) scores versus placebo. G/G versus non-G/G patients had greater improvement with iloperidone versus placebo in PANSS, BPRS and CGI scores.


CONCLUSIONS
The relative treatment benefit of iloperidone compared with placebo in patients with schizophrenia is enhanced in patients homozygous G/G for the rs1800169 polymorphism.
Lavedan
Christian
C
Vanda Pharmaceuticals Inc, 9605 Medical Center Drive, Suite 300, Rockville, MD 20850, USA. christian.lavedan@vandapharma.com
Volpi
Simona
S
Polymeropoulos
Mihael H
MH
Wolfgang
Curt D
CD
D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D020934:Ciliary Neurotrophic Factor / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007555:Isoxazoles / Q000627:therapeutic use*; D008297:Male; D010880:Piperidines / Q000627:therapeutic use*; D010919:Placebos; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D044469:Racial Groups; D012559:Schizophrenia / Q000188:drug therapy* / Q000235:genetics*; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D020934:Ciliary Neurotrophic Factor; D007555:Isoxazoles; D010880:Piperidines; D010919:Placebos; C081732:iloperidone