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Nonsense, Sense, and Antisense

© John McManamy

"Antisense technology is the ultimate magic bullet."

The following is an expanded version of a piece that first appeared in my Depression and Bipolar Weekly:

A wide-eyed first-year medical student eagerly listens to his teacher and faithfully records: "The liver is the most complex organ in the body."

This draws a round of hearty laughter from the audience. The venue is the National Depressive and Manic Depressive Association Conference in Boston, and the speaker is Charles Nemeroff MD, PhD of Emory University.

"How gullible was I," he acknowledges. The liver, he goes on to say, has the same composition no matter which way you slice it, while the brain's various parts are as different from each other as the liver is from the kidneys.

"Ninety percent of what we know about the brain," he tells us, "we've discovered in the last ten years."

One can hear some oohs and ahs from the audience, as well as sense a collective feeling of recognition. Of course, five hundred people are thinking at once, this explains everything, doesn't it?

Meanwhile, this new knowledge is on its way to finding new applications. For instance, PET scans may be able to tell doctors which drugs to prescribe, say an SSRI such as Paxil vs a novel agent such as Remeron. My notes say something about serotonin transporter sites, which some of you no doubt have written your masters thesis on.

Then there is the chemical dance of the reuptake process, which leads to the number one cause of SSRI noncompliance - sexual dysfunction. Why not, Dr Nemeroff asks, combine an SSRI with a "blocker" to block the side effect?

The most exciting stuff is saved for last - the possibility of finding the genes responsible for depression and bipolar and coming up with effective treatments. Ninety-six to 97 percent of human genes are identified in the chimpanzee, a species which does not suffer from bipolar or depression. So by process of subtraction we should come up with candidate genes fairly soon.

In another seminar, Dr Robert Lenox of the University of Pennsylvania reels off the locations of the likely bipolar genes - chromosome 18, chromosome 12, chromosome 4, chromosome 22 ...

Meanwhile, Dr Nemeroff is talking about "antisense technology." Basically, RNA acts as a messenger that is involved in creating disease-causing proteins. Traditional drugs are made to interact with these proteins. By contrast, antisense drugs are designed to inhibit the production of these proteins by wrapping itself around the messenger RNA.

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