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Friday, February 6, 2009

Howard McLeod, University of North Carolina, Chapel Hill - “Using the Genome to Optimize Drug Therapy”

“A surgeon who uses the wrong sde of the scalpel cuts her own fingers and not hte patient.
If the same applied to drugs they would have been investigated very carefully a long time ago.”
Rudolph Bucheim. (1849)

The clinical problem: Multiple active regiments for the treatment of most diseases. Variation in response to therapy, unprecedented toxicity + and cost issues! With choice comes decision. How do you know which drug to provide.

“We only pick the right medicine for a disease 50% of the time”. Eventually we find the right drug, but it may take 4-5 tries. Especially in cancer.

“toxicity happens to the patient, not the prescriber”

[Discussion of importance of genetics. - very self-deprecating humour... Keeps the talk very amusing. Much Nature vs. Nurture again]

“Many Ways To Skin a Genome”. Tidbit: Up to half of the DNA being meausred can come from the lab personal handling the sample. [Wha?] DNA testing is being done in massive amounts: newborns, transplants..

“you can get DNA from anything but OJ's glove.”

We also see applications of genetics in drug metabolism. Eg, warfarin. Too much: bleeding, too little; clotting. One of only two drugs that has it's own clinic. [yikes.] Apparently methadone is the other. Why does it have its own clinic? “That's because this drug sucks.” Still the best thing out there, though. Discussion of CYP based mechanisms and the Vitamin K reductase target. Showed family tree – too much crossing of left and right hand...

Some discussion of results – showing that there are difference in genetics that strongly influences metabolism of warfarin.

Genetics is now become part of litigation – Warfarin is one of the most litigated drugs.

We need tools that translate genetics in to lay-speak. IT doesn't help to tell people they have a CYP2C*8.. they need a way to understand and interpret that.

If we used genetics, we'd be able to go from 11% to 57% of “proper doese” at the first time with warfarin.

Pharmacogenomics have really started to take off and there are now at least 10 examples.

What is becoming important is pathways... but there are MANY holes. We know what we know, We don't know what we don't know.

We can do much of the phenotyping in cell lines – we can ask “is this an inheritable trait?” This should focus our research efforts in some areas.

Better systematic approach to sampling patients.

What do we do after biomarker validation? Really, we do nothing – we assume someone else will pick it up (Through osmosis... that's faith based medicine!) We need to talk to the right people and then hand it off – we need to do biomarker-driven studies with the goal of knowing who to hand it off too.

Take home message:

Pharmacogenetic analysis of patient DNA is ready for prime time.

My Comment: Very amusing speaker! The message is very good, and it was engaging. The Science was well presented and easily understandable, and the result is clear: there's lots more room for improvement, but we're making a decent start and there is promise for good pharmagenomics.



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