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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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July 9, 2002

Maybe They Can Formulate It in Madelaines

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Posted by Derek

There's a report today that an Alzheimer's medication seems to help memory function even in people who don't have the disease. As reported in Neurology, pilots using a flight simulator performed better when repeating tasks learned while taking Pfizer's drug donepezil (Aricept - it's actually an Eisai drug that Pfizer licensed.)

Before anyone gets too excited, the changes, although statistically meaningful, were small. A quote in the NY Times science section today compared the size of the enhancement to that of the deficit imposed by, say, a hangover. For some people's hangovers that's probably an impressive yardstick, but it was meant to suggest a modest improvement. Still, there's an interesting concept here, and it's been much on the minds of researchers over the years.

Some background: Aricept is a cholinesterase inhibitor, which basically replaced the first such compound on the market, Tacrine (which had sporadically nasty liver toxicity.) As far as I know, it has most of the market for that mechanism. Other companies (such as Bayer) have tried to bring compounds to market, but getting them right can be difficult. After all, a good example of a truly effective, fast-acting cholinesterase inhibitor is nerve gas. You want to back away from that kind of activity for Alzheimer's patients, of course, but side effects are still possible.

And even if the compound is clean, there's only so much a cholinesterase inhibitor can do for someone with Alzheimer's. At best, you can hope to slow the progression of the disease a bit, and response rates vary. Some patients probably show improved quality-of-life, but others are likely wasting their time and money. The whole basis of cholinergic therapy for Alzheimer's (a field I've worked in,) is fairly crude: jacking up the levels of the neurotransmitter acetylcholine across the board. Admittedly, this idea can work for other neurotransmitters (dopamine in Parkinson's disease, or serotonin in depression.) But (just as in the Parkinson's case) it doesn't address the underlying disease; it just tries to ameliorate the symptoms while things get inexorably worse.

But what about people who don't have Alzheimer's? As mentioned above, I can tell you that that question has crossed the mind of everyone working in the memory-enhancement field. What if your drug makes diseased brains more normal, and normal brains. . .better than that? The FDA hasn't dealt much with such issues, understandably, and I can't think of a company that's had the nerve to ask them. But while the market for an effective Alzheimer's drug would be large, the market for a safe memory drug for the general population could be gigantic. The benefits could be similarly huge.

The closest analogy I can think of is the obesity market. Right now, there's no good drug therapy for obesity, period, although people spend billions of dollars trying to say otherwise. Most people's idea of a good obesity drug would be the Magic Pizza Pill - you know, the one you take, and then you can eat all the pizza you want. Don't hold your breath for it; I don't think it's possible. But even a reasonably effective obesity drug would be a huge seller.

And the unspoken assumption about any such drug is that a significant number of the people taking it would not necessarily be all that obese. There are certainly enough obese people to make for a successful drug, and more coming all the time, but there are plenty of folks who would just want to look a little better. Nothing wrong with that, since even modest weight loss is very likely a good thing. But the regulatory assumption is that weight-loss drugs would go primarily to the morbidly obese, whose lives are in more immediate danger. That's not nearly as large a potential market (although at the rate we're going, it could end up being one.)

Companies working on memory-enhancing drugs have had the same thoughts, and done the same math. That said, many of the current therapies being tried for Alzheimer's aren't in this category, since they're more specifically aimed at what seem to be the disease processes. Even among those groups working on memory in general, the odds of dramatically improving function are low. You'd figure that the system is fairly well optimized by now. But what if you did find one? How many people would line up for it? It would be an off-label indication with a vengeance.

I doubt if I would take it myself, not until plenty of others had done so for at least a few years. I'm very nervous and twitchy about CNS medications in general (probably from having worked in the field, as I mentioned!) I have no desire to mess with my brain chemistry unless absolutely necessary.

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