SINGLE NUCLEOTIDE POLYMORPHISM FOR CORTICOTROPIN-RELEASING HORMONE 1 RECEPTOR (CRHR1), A BIOMARKER FOR PREDICTING DRUG RESPONSE TO FLUOXETINE AND DESPIRAMINE THERAPY
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UCLA Technology Available For Licensing |
BACKGROUND:
Depression is a common and complex disorder involving the interplay of genetic and environmental factors. The disorder affects 10% of males and 20% of females and has a point prevalence of 3%. Its cost to the U.S. economy exceeds 100 billion dollars per year. Over twenty drugs are approved by the U.S. Food and Drug Administration for treatment of depression, each one with efficacy of approximately 60%. Various subgroups of patients respond differently to each drug so that if multiple trials are conducted, eventually 85% of patients will respond. Because there are no clinical or biomarker predictors of treatment response, the assignment of a depressed patient to a drug is based solely on chance or on attempts to minimize side effects that are more likely to occur with a specific medication. This random approach in therapy selection can be detrimental to a patient's well being if the prescribed drug doesn't produce a therapeutic response while generating undesirable side effects. Further, this lack of response can negatively affect a patient' compliance to future therapy. In order to increase effectiveness in treatment, efforts are underway to identify genetic predictors of treatment response.
INNOVATION:
Researchers at UCLA have first mapped the corticotrophin-releasing hormone receptor (CRHR1) in the brain in 1994. Since then, the receptor has been implicated in the response to antidepressant treatment. In a randomized, placebo lead-in, double-blind study of 80 depressed patients undergoing active treatment of fluoxetine or desipramine for eight weeks, the researchers tested for haplotype association between CRHR1 and response to treatment. The results of this work suggested that response to antidepressant treatment is heterogeneous and that a specific haplotype of CRHR1 and possibly other genes in stress-inflammatory pathways are involved in the response to antidepressant treatment. The invention involves a specific SNP that can be detected in exfoliated or distributed cells using genetic analysis techniques.
POTENTIAL APPLICATIONS
- The biomarker can be used to predict response to antidepressants (specifically
fluoxetine or desipramine) prescribed for anxiety and depression. It has applications
for use in:
- Therapy selection; and
- Stratifying patients for clinical trial testing of new antidepressants.
ADVANTAGES
- The invention has been validated in a clinical study and the specific SNP has been mapped;
- Nucleic detection in exfoliated or distributed cells can be scaled to high-throughput; and,
- CRHR1 is a target receptor for several antidepressants in the clinic.
RELATED ARTICLES
Mol Psychiatry. 2004 Dec;9(12):1075-82. Association of a corticotropin-releasing hormone receptor 1 haplotype and antidepressant treatment response in Mexican-Americans. Available at Nature.com
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email: ncd@research.ucla.edu
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NCD URL: http://www.research.ucla.edu/tech/ucla05-056.htm
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UCLA Technologies Available for
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keywords: diagnostic depression anxiety snp single nucleotide polymorphism crhr1 corticotropin treatment response antidepressant anti-depressant prozac fluoxetine despiramine
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