IRA FLATOW, host:
This is Talk of the Nation: Science Friday. I am Ira Flatow. Like a spreading weed, Alzheimer's disease attack sufferers by clogging the brain's once spindly and delicate neurons with an overgrowth of protein. The signature plaques entangles damage the brain's communication structures, and block its information highways. Patients lose their memory, their ability to think and care for themselves, eventually they die. But my next guest, says that an over-the-counter supplement, a vitamin can cut through that snarled protein mess at least in laboratory animals.
His studies show that large doses of vitamin B3 can protect mice with Alzheimer's from memory loss and mental decline, by blocking one kind of neuron damage, that caused by the protein tangles. The treatment works so well in fact, that the Alzheimer's mice can act and perform just like mice that don't have the disease at all. His study is published in the journal Neuroscience. Joining me now to talk about it and maybe possible some new human trials in the works, is my guest Ken Green, a research scientist at the University of California, Irvine. Welcome to Science Friday, Dr. Green.
Dr. KEN GREEN (Research Scientist, University of California, Irvine): Thank you. Hello. It's great to be speaking with you.
FLATOW: You're welcome. Now you've found that a - the vitamin prevents the symptoms of Alzheimer's in mice, how did you come about to test this product?
Dr. GREEN: Well, we were interested in nicotinamide, not because it was a vitamin, but because its pharmacological abilities to inhibit a group of enzymes known as Sirtuins. And these Sirtuins are implicated in longevity or living longer successfully. And of course, with Alzheimer's disease being a disease of aging, we wanted to see what happens to the disease progression when we're able to modulate these pathways associated with aging. And so, that's why we selected this compound in the first place.
FLATOW: Mm-hmm. So, you found some mice - you genetically engineered mice to have a mouse version of Alzheimer's?
Dr. GREEN: Exactly, we have some transgenic mice, and these are normal mice that we have taken the human genes that give rise to the proteins…
Dr. GREEN: Which aggregates in the (unintelligible) brain, and we've injected those into the mouse eggs…
Dr. GREEN: That creates a new mouse, and as this mouse ages it produces these proteins. And they form the same sort of pathology that you find in the human brain. They develop these extracellular amyloid beta plaques, and also these intraneuronal aggregates composed of tau protein...
Dr. GREEN: Which enables these tangles. And what we find for these mices as they age and as they develop these two pathologies, they get cognitive impairment at the same time.
FLATOW: And you then gave the mice's this vitamin B3 right in their water?
Dr. GREEN: Exactly, exactly. This stuff is very easy to give, which makes (unintelligible) 3:26 a lot easier. And we very simply just put it in their drinking for four months as they aged. And at the end of that four months, we tested their memory. So, we wanted to see what effect it had on their cognitive abilities.
FLATOW: Mm-hmm. And you were surprised by the results?
Dr. GREEN: I was very surprised. It has been far more successful and encouraging than I could have imagined. And when we looked at the mice, we found that they performed at the same level as a mouse that is not programmed to develop Alzheimer's disease.
Dr. GREEN: It completely prevented the cognitive deficits associated with pathology.
FLATOW: Mm-hmm. And you actually gave it to normal mice, and it improved their behavior too?
Dr. GREEN: Exactly, that was also quite surprising.
Dr. GREEN: So, it also suggests that this stuff could be good for healthy people as well, and it can improve memory function. So, it looks like it can be cognitive enhancing of its own right, but especially beneficial in a neuro-degenerative disease such as Alzheimer's.
FLATOW: Mm-hmm. And of course when people hear about this study, they're going to be flooding the health-food stores.
Dr. GREEN: Yeah.
FLATOW: Is there a danger to vitamin B3?
Dr. GREEN: Yes, there certainly is. If you take it in high doses, there can be liver toxicity associated with this, and the sort of doses we're using, because we're using it as a pharmacological agent rather than a vitamin, you're getting towards those sort of doses.
Dr. GREEN: And so, I would certainly not recommend the people go out and start taking high doses of the stuff, until we've looked at it more careful in humans, to work out what a safe and effective dose could be.
FLATOW: Are there studies planned for humans?
Dr. GREEN: Absolutely. We're recruiting for clinical trials at the moment here at UC, Irvine. And we want to get started on those as quickly as possible, so we can find out if it's as effective in humans as it's shown to be promising in mice.
FLATOW: Mm-hmm. You've also done work with Omega-3s?
Dr. GREEN: Yes, yes. We're particularly interested in looking at safe, effective therapies that people can take, that can affect their likelihood to develop Alzheimer's disease. And it turns out that people can actually do a lot for themselves.
Like heart disease, you can change your lifestyle to prevent neuro-degenerative diseases, in particulatre Alzheimer's Disease, and dietary factors and environmental practice can play large roles, and one of the big dietary factors is the daily intake of Omega-3, poly-unsaturated fatty acids such as DHA, docosohexanoic acid. And that works by reducing the amyloid beta peptide in the brain.
FLATOW: Mm-hmm. Can other vitamins possibly have an effect on Alzheimer's?
Dr. GREEN: Other what, sorry?
FLATOW: Other vitamins.
Dr. GREEN: Other vitamins. Well, so there'd been a lot of trials with vitamins over the years, and they have shown a lot of promise and people has done a lot of research. But unfortunately at the moment, a lot of it has shown that it doesn't have an effect in the clinic.
Dr. GREEN: And other vitamins such as B6, and B12, and E, haven't been successful in clinical trials.
Dr. GREEN: And that by no means, means that Vitamin B3 is not going to be successful, because they work in completely different ways.
FLATOW: How does B3 actually work on those tangles? It doesn't appear from your research that it works on all of the problems in the brain, the plaques, but it does work on the tangles.
Dr. GREEN: It does. It seems to be very specific in what it does. And it's able to stimulate the neurons to degrade tau, once it's become phosphorolated at a specific residue. And the normal function of this tau protein in neurons is to help transport things from the cell body, all the way to the extremities. Neurons are very long cells.
Dr. GREEN: They have an effective transport system to survive, and send energy and proteins from one end to the other. And the tau sort of strengthens this highway. And when it becomes phosphorolated, it falls off this highway and the highway begins to break down, so you can't transport stuff effectively anymore. And what the next (unintelligible) does, is it's able to get rid of this phosphorolated tau once it's produced, so the highway remains strengthened. And so that transport can continue to occur.
FLATOW: Hmm. Mm-hmm. That's quite interesting. When will - are you're looking for volunteers for your human studies?
Dr. GREEN: Oh, we are absolutely. They have to be in the local area, Orange County. They need to be able to get to where we are in Irvine, and we're - we need around 50 to 70 patients for six months' clinical trial with nicotinamide.
FLATOW: Well, we have a huge audience in your neighborhood.
Dr. GREEN: I hope so, I really do. That would be great.
FLATOW: Huge audience in your neighborhood. And they can go to Science Friday and learn how to reach you there also. Are there foods that naturally contain Vitamin B3?
Dr. GREEN: Well, there are other foods, meat, fish, beans, (unintelligible) and potatoes. But quite honestly, the sort of levels that you're going to find in these foods probably aren't sufficient to have a big effect.
FLATOW: Hmm. You - and once again, you warned that taking too much B3 can be toxic?
Dr. GREEN: Absolutely, this is why we're doing the clinical trials to work out a safe and effective dose. I mean, if we have patients here on known doses, we can monitor liver function, and make sure that they're looking healthy. Now, having said that, there was a study that came out a couple of years ago that looked - followed a group of elderly people for several years, and they looked at those patients that developed Alzheimer's Disease versus those that didn't, and then looked at all their different dietary intakes.
Dr. GREEN: And they found an inverse risk associated with developing Alzheimer's Disease with niacin, which is another form of Vitamin B3. And these are people taking in a sort of health-food supplement form.
Dr. GREEN: And so, there is some, you know, fairly promising evidence out that for even low doses that you'd find in your health store at the moment, could be protective.
FLATOW: Right. How close is the animal model to a real human model of Alzheimer's?
Dr. GREEN: It - this is about as close as we can get. But it's not perfect. It's a big leap from a mouse to human. But what - the problem with Alzheimer's disease is it's a very complicated disease, it's very widespread. It affects many areas of the brain. We have multiple pathologies, there's tau pathologies, there amyloid pathology, we get inflammation oxidative damage, and so it's very difficult for one therapy in particular to be able to cure all the different things that are going wrong.
And what's great about something like nicotinamide, and DHA, and some of these other things, is that we can combine them together to try and target multiple pathologies simultaneously. And that's probably what is going to be the most effective in the future, is putting multiple different approaches together.
FLATOW: Mm-hmm. Mm-hmm. And what other effects did it have on the brain, did it enhance the structure of the brain itself?
Dr. GREEN: No, not so much. We were looking mainly at the protein level at the biochemical level, and the effects appeared to centralize around these microtubule highways, and they up regulated a number proteins that are associated with the stability of these highways.
FLATOW: Mm-hmm. And even - and it's interesting that even in the normal mice, you - their memories were enhanced, correct?
Dr. GREEN: Exactly. I mean, it just shows that this stuff has a beneficial effect in healthy mice, as well as Alzheimer's, you see, it's probably through similar mechanisms. You know, you strengthen your highways and normal neurons, they probably work more effectively than if you haven't.
FLATOW: Mm-hmm. The fact that this is something that's a generic form, that you know, the drug companies are not going to invest in I imagine in research again, because it's freely available.
Dr. GREEN: Well, it's freely available, and you know, part of our research is to highlight things like this which people can go out and take, once we've discovered if it's effective. But what we do know is that it's - it inhibits this class of enzymes known as situins. So, if it turns out perhaps that nicotinamide isn't as effective in humans, we could now use this family of enzymes as a new drop target to develop new small molecular inhibitors that do the same job, but more effectively at lower doses.
Dr. GREEN: And it's something that drug companies could be interested in.
FLATOW: Mm-hmm. Is it necessary to do anymore animal testing, or do you just go right on to human testing?
Dr. GREEN: Well, we're going right on to human testing, because it's something that's freely available, of course, if this was an unknown compound, we'd have to do a lot more safety profiling, before we could make that leap. And so in many ways, this make our job a lot quicker by using things that are already out there in the population.
FLATOW: Hmm. So you don't have to go to the phase-one trial, because it's been out there awhile?
Dr. GREEN: Exactly. So we can go straight to phase two.
FLATOW: And are you looking for Alzheimer patients?
Dr. GREEN: Absolutely, it has to be mild to moderate, the more mild, the better. The problem with Alzheimer disease is once you have it, it's very hard to see how we're going to be able to reverse it...
Dr. GREEN: Because by the time a patient who has cognitive decline is presenting with symptoms, they already have a great deal of pathology in their brains. They already have a great deal of neuronal loss. And ideally what we want to be able to do is to prevent people from developing the pathology under neuronal loss in the first place.
Dr. GREEN: But that's very hard to do in a clinical trial, because we can't identify the people who are going to develop Alzheimer's disease in order to prevent them.
Dr. GREEN: So we need to, you know, fine pick the best approaches we have, and try them in people who already have pathology, and hope that we see an effect.
FLATOW: Well, good luck to you, doctor.
Dr.GREEN: OK. Thank you very much.
FLATOW: And hopefully, we'll be able to send some patients your way.
Dr. GREEN: I hope so, thank you very much.
FLATOW: Your welcome. Ken Green is a research scientist at the University of California at Irvine, and if you want you get in on his study, contact him there or go to our web page and we'll send you to a link in that direction.
We're going to take a short break and when we come back, we're going to switch gears a little bit and talk about the human genome, sequencing the human genome and how they have sequenced the first person with cancer, and the differences that knowing what the genes were in the cancer person tells us about, hoping to diagnose it, later on. So stay with us, we'll be right back after this break.
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FLATOW: I am Ira Flatow. This is Talk of the Nation: Science Friday from NPR News.
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