Personalized Medicine

This presentation is based on a patent application on personalized medication held by George Mason University. Scientists and government organizations have free access to this patent

Farrokh Alemi, Ph.D.Manaf ZargoushHarold Erdman, Ph.D. Igor Griva, Ph.D.Charles H. Evans, Jr., M.D., Ph.D. Jee Vang, Ph.D.Manabu Torii, Ph.D.Steven Epstein, M.D.

Military service Industrial manager, polite, defines himself a

“medieval knight.” First depression episode at 26, treated with

clomipramine, dose unknown. At 30 married with a daughter At 45 return of depressive symptoms, treated

with fluvoxamine 200–300 mg and mirtazapine 15 mg

Depression continues, loss of interest in work, difficulty with bi-polar daughter

Loss of daughter, divorce and loss of work At 48, suicide

Beyond Efficacy: The STAR*D Trial. By Thomas R. Insel Am J Psychiatry. available in PMC 2006 September 30.

Read more: http://www.time.com/time/health/article/0,8599,1905083,00.html#ixzz0kWKdxlNH

Response to medication▪ Quick Inventory of Depressive Symptomlogy

<=5Predictors of response

▪ SNP▪ Allele

Most likely predictors▪ Serotonin transporter gene SLC6A4 ▪ Serotonin transporter polymorphic region

5HTTLPR

Source: http://www.youtube.com/watch?v=IMeJA_inoEM

“… limited clinical utility in

matching antidepressants

to patient’s genetic profile”

Peters EJ, Slager SL, Kraft JB, Jenkins GD, Reinalda MS, McGrath PJ, Hamilton SP. Pharmacokinetic genes do not influence response or tolerance to citalopram in the STAR*D sample. PLoS One. 2008 Apr 2;3(4):e1872.

12 month follow up post experimentation

Careful baseline and exit data4300 patients 1933 with genetic data

430,198 SNP per case 25 likely SNP

Garriock HA, Kraft JB, Shyn SI, Peters EJ, Yokoyama JS, Jenkins GD, Reinalda MS, Slager SL, McGrath PJ, Hamilton SP. A genome wide association study of citalopram response in major depressive disorder. Biol Psychiatry. 2010 Jan 15; 67(2): 133-8.

Test statistical significance of findings among the K most similar cases

Nearest defined?▪ Euclidian distance (percent of features

matched)▪ CART classification

Statistical test?▪ CUSUM▪ Exponentially weighted cases

Test statistical significance of findings among the K nearest neighbors

Nearest defined?▪ Euclidian distance (percent of features

matched)▪ Severity of illness

Statistical test?▪ CUSUM▪ Exponentially weighted cases

Hypothetical Data

Hypothetical Data

Hypothetical Data

Non

responder

s

Not sure

Response to citalopram is predictable

A large effect size is observedCombination of genes matterSubgroup of patients have different

predictors