Hearing the words "cure" and "Alzheimer's" together in the same sentence would be a medical miracle for the five million americans living everyday with this devastating condition. In the meantime, the national institute on aging will soon recruit a small number of patients to test a new drug that researchers hope will reverse the damage that Alzheimer's has already done.
Muriel Levy and her 79-year-old husband Gordon Hallerman have been married for 10 years. Second marriages for both.
Hallerman's good health faded two years ago when he was diagnosed with Alzheimer's.
"There are times when I would walk into the kitchen and then not remember what it is I was going in there for," Gordon Hallerman told Ivanhoe.
"Gordon is doing well and we work together. But certain things he was able to do he could no longer do," Muriel Levy told Ivanhoe.
But what if he could reverse what Alzheimer's has taken away?
"What we've been studying is a new medicine that helps the brain to recover from injury," Sam Gandy, M.D., PhD, Director of the Center for Cognitive Health at Mt. Sinai School of Medicine told Ivanhoe.
Dr. Sam Gandy explores the Alzheimer's brain ─ the plaque build-up that destroys the nerve cells responsible for memory.
"What this medicine does is to help form new brain cells," explained Dr. Gandy
The drug doesn't have a name yet- only a number, BCI-838 ─ and must undergo clinical trials in the elderly.
"We are aiming at people who perhaps already have some problems," said Dr. Gandy.
For Hallerman, who sang professionally, this is a first — a drug aimed at patients just like him.
"It could be a life change for us," said Levy.
Doctor Gandy and his team have tested BCI-838 in mice, and have also tested the drug for safety in humans, in a very small group of young, healthy adults. Gandy says the phase one clinical trial will recruit older adults who have mild Alzheimer's or mild cognitive impairment. When the trial is ready to begin enrollment, it will be posted on www.clinicaltrials.gov – and anyone interested can check the site for updates.
BACKGROUND: As the most common cause of dementia, Alzheimer's disease occurs when brain cells degenerate and die. As the brain cells die, the brain actually shrinks. This causes a steady mental decline in overall mental functions as well as memory. Alzheimer's first destroys cells in the hippocampus causing short-term memory loss, followed by a decline of language skills and judgment which are controlled by the cerebral cortex.
CAUSES AND PREVENTION: There are two notable abnormalities of this disease: plaques and tangles. Plaques are beta-amyloid protein clumps that form outside and around neurons, interfering with cell-to-cell communication. Tangles refer to threads of the protein, tau, that tangle inside of the brain and nerve cells. While Alzheimer's is not a normal part of aging, the risk of getting it increases after 65. Family history and genetics can play a small role in developing Alzheimer's; however, lifestyle and environmental factors are just as prevalent in increasing risk. Although these factors are not conclusively proven to reduce the risk of existing Alzheimer's, not maintaining blood pressure, cholesterol, controlling diabetes, smoking or lack of healthy diet and exercise can adversely affect your chances of getting it. Mental and social stimulants have been associated with prevention of Alzheimer's, such as: mentally challenging activities (reading, games), playing a musical instrument, and frequent social interactions
NEW DRUG TRIAL: Created as a pro-drug for the active agent BCI-632 for treatment-resistant depression, BCI-838 was studied for safety, tolerability, pharmacokinetics, and pharmacodynamic effects in healthy male and female subjects. While it is similar to ketamine in that it creates early antidepressant responses, it differs in that it has a better safety profile and less liability. Its neurogenic effect on the hippocampus may make it an appropriate treatment for mood or cognitive disorders. Sam Gandy, M.D., Ph.D., Director of the Center for Cognitive Health at Mount Sinai School of Medicine, published a study with the Institute of Medicine, showing the effect of BCI-838 in mice which resulted in improved learning and anxiety behaviors, as well as exaggerated neurogenesis. For more on Dr. Gandy's study, visit: http://www.iom.edu/~/media/Files/Activity%20Files/Research/NeuroForum/2013-APR-8/Presentations/Session%201-4%20Samuel%20Gandy.pdf.
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Sam Gandy, M.D., Ph.D., Director of the Center for Cognitive Health, Mt. Sinai School of Medicine, talks about a new drug that could reverse the damage of Alzheimer's disease.
Interview conducted by Ivanhoe Broadcast News in September 2014.
What exactly is it and is this a medical breakthrough for Alzheimer's?
Dr. Gandy: So what we've done in the studying in what we think is a new medicine that helps the brain to recover from injury. This is a medicine that we started studying several years ago because it can help the pathology of Alzheimer's disease. Then we went on to move it to test it in to animal models and there we found not only did it reduce the pathology but it helped the brain recover. There's a part of the brain that's responsible for memory called the hippocampus and what this medicine does is to help form new brain cells, new nerve cells in the hippocampus. And during Alzheimer's disease the hippocampus is one of the places that's really devastated by nerve cell loss. So what we're hoping is that at early stages or even before Alzheimer's we can use this medicine to help the brain withstand that insult, withstand that injury and perhaps even recovery from the injury of Alzheimer's disease.
This is huge you're saying not only does this particular medicine stop the disease from progressing but maybe even reverse?
Dr. Gandy: Well those are the sort of effects that we're seeing in mice, I'm careful not to get too carried away until we see human results but we know the medicine is safe in young healthy people so it has been tested for safety in young healthy people. So we're moving on soon to test it in an elderly population for a longer period of time. For Alzheimer's disease our trials of new medicines usually take several years, up to three years. The medicine has only been tested for safety for a few weeks so we need now to do safety test for those three years to be sure it's safe before we then do a large test with several hundred patients. But we think we're on the way towards important clinical trials here.
So at this point you have a handful of people that's actually older people now with Alzheimer's actually using this particular medicine.
Dr. Gandy: Those are the trials that we are starting now that's right, we're just getting that underway they haven't actually started taking medicine yet. But that's the next step. The first safety step is to be sure the drugs, any new drug is well tolerated in young healthy people. And that's been achieved, that seems fine with Alzheimer's disease since we want to test over a long period of time we need to now do a safety test in both an elderly population, an older population and for a longer period, for at least a few months to be sure it's going to be safe. In order to actually test to see whether it's going to be useful for Alzheimer's we then need to do a study of about three hundred patients over about a year and a half. So that's where we're ultimately headed to see whether this is it going to be meaningful. One of the real sort of novelties that we see is that this medicine targets people, may help people who already have the disease. A lot of the newer medicines that are being developed now are being aimed toward prevention they're being aimed at earlier and earlier stages though we have millions of people who are already affected. And obviously people who are at very late stages I think this isn't going to help them a lot. But hopefully in people who are at just the very early stages we can preserve their independence and that sort of thing for longer periods of time.
Talk about the devastation of Alzheimer's like you mentioned millions of people are dealing with this.
Dr. Gandy: Yeah, Alzheimer's disease is really going to break the bank of the Medicare and Medicaid system in this country. In fact it threatens the economies of most developed countries in which the life span is past age seventy. Over age eighty five, half of the population has a dementing illness usually Alzheimer's disease. So if most of us live to eighty five one of us is likely to get Alzheimer's disease. That means for most people one parent is likely to get Alzheimer's disease but that doesn't happen in every family but statistically speaking that's the, that's the prediction. If both parents live past age eighty five one would have Alzheimer's disease.
Wow, and of course we know what it does to a family; the effects of seeing your loved one, the illnesses affects the entire family. Grandchildren, wives, children, and adult children it's hard.
Dr. Gandy: It's a devastating disease if the person who has the disease just sort of slowly disappears from the family and his or her community, if they're lucky. Some people actually the disease moves even more rapidly than that. But the disease is devastating to the families. The folks with the disease aren't, often aren't safe to be left alone. They have to have 24 hour care or 24-hour supervision of some sort and that happens early in the disease. And people are living longer now healthcare is better than it used to be so people with Alzheimer's disease can live fifteen or twenty years in the state of progressive disability.
The people that you mention for the three or so for the trial is that something that you're looking at here at Mt. Sinai or is this part of the national three hundred number?
Dr. Gandy: We envision that to be part of a national group. There's a group that's based at the National Center of Aging who has expressed an interest in collaborating with us to test this in a larger population. And then part of the reason is that by tapping that larger population we can recruit those three hundred subjects very quickly because since the studies already a year and a half you don't want to spend six months or a year getting those three hundred in.
What are you looking for, somebody early in their disease is that what you are looking for?
Dr. Gandy: Mild disease primarily, people who are still living at home who primarily aren't yet in nursing homes but who are sufficiently impaired, they're functioning is not up to the way it used to be and that they've perhaps lost independence or maybe getting even just a little forgetful. You know we want to be sure that we have the diagnosis right; we want to make sure that they have Alzheimer's disease as well. They'll need to be assessed by an expert to be sure they meet those criteria. But for the very modest stage of which we can be sure that's what's going on.
And of course you said just a little bit of forgetfulness, is that still what we're looking at in terms of the signs and symptoms that this may be happening to your loved one, is that usually where you start?
Dr. Gandy: Forgetfulness is sort of the classical part of Alzheimer's disease. These people with the disease lose the ability to form and retrieve new short-term memories, their long-term memories are often intact but their short-term memory fails. They might be able to tell you in great detail about their childhood but they can't tell you what they ate for breakfast, that sort of thing or they can't tell you the date. Other things are involved as well as the disease progresses changes in navigation, confusion, getting lost and being familiar with environments, personality changes and that sort of thing as the disease progresses. Virtually everyone will have some of these symptoms as the disease progresses in to you know the moderate and late stages.
And then of course then you become tested and you get the scan and then you can see the activity from brain scans?
Dr. Gandy: That's right. It's now possible to visualize the buildup of Alzheimer's pathology, these structures called amyloid plaques. We can see them during life now. For many years we were only able to see them at autopsy it's now possible to see them during life with a brain scan. That's how we confirm the presence of Alzheimer's disease now.
Talk about the drug, what's the name of it and how is it – what is this drug that you're talking about?
Dr. Gandy: Well it only has a number now it doesn't have an actual name yet; it's called BCI-838. It's in a paper that we've recently published in a journal called Molecular Psychiatry. It sticks to the surface of the nerve cells and blocks a particular protein called the receptor. And this particular receptor is called a glutamate receptor; glutamate is one of the chemicals that neural cells use to talk to each other. We don't understand exactly how the binding of this drug to this receptor, to this cell surface substance triggers this process of new birth of new nerve cells. However we do know now as our lab and from several other labs that surprisingly this is now the fourth medicine that can stimulate birth of new nerve cells that helps mice that have a model of Alzheimer's disease. We've primarily been focusing on the pathology until now but up until these last four drugs we now see the ability to perhaps stimulate the birth of new nerve cells and help the brain to withstand the pathology, to continue to function normally even though there's plaques and tangles building up.
Why do you call a different number than this GLUR-231?
Dr. Gandy: So the GLUR-23 is actually the name of the protein on the surface that it sticks to. So the drug is called BCIA-38. The MGLUR-23 is the actual name of the receptor on the surface that it binds to. So they're related, the receptor is called MGLUR-23 and the actual drug is called BCIA-38.
Early on you mentioned that there are promising drugs to prevent Alzheimer's at this point. Is this happening right now?
Dr. Gandy: Well they are being assessed and they're promising. These are medicines that are aimed at preventing the buildup of this material called amyloid that forms plaques and there are trials now giving this medicine when people have perhaps even no changes at all but are found to have positive brain scans. Now that we have these brain scans that people develop the pathology perhaps ten – twenty years before their first symptom. So by focusing on people who already have symptoms as we have done for these many years we're sort of already you know many decades into the process and didn't really realize it until we had the scans. So the prevention trials are now to find people who have positive scans but don't really have much in the way of symptoms. They start to give them a chemical and an antibody and immune molecule to help them break down the amyloid, to break down the plaques so that hopefully they never get the symptoms. We don't know yet whether that's going to work but there are a number of trials like that going on now. That's where most of the new drug research is headed right now in this prevention area. And one of the sort of unusual things about the medicine that were working on is any people who perhaps already have some problems.
There's a lot going on and Alzheimer's.
Dr. Gandy: There's a lot of work, there's a lot yet to be done. It's a huge problem we've never developed a medicine like this, it's not through like cancer or epilepsy or pneumonia it's a different sort of problem but I mean I'm convinced that we will be beat it eventually. I think it's just a matter of getting the right the right drug and at the right time and we'll be able to prevent it. I don't think will be cursed with this for the rest of human civilization.
I'm trying to get an understanding of what your role is of all this, are you working with the collaboration of other doctors around the country, how is Mt. Sinai and you in particular playing into developing this.
Dr. Gandy: We began with a different related developed drug that we bought from a store. It had been developed by one of the drug companies that didn't look promising for a drug. And our very, very first studies we use that sort of compound. That also stuck to the MGULR-23 but was not 838 it was a different number. But it didn't look promising for medicines it looked like it was going to have side effects. We found that the drug, the BCI-838 that we are using had been made by a different drug company, a Japanese chemical called Takata and we were able to secure permission from Takata to get that drug and get the drug to test it. So we'll now continue to work with them to do the clinical trial but the trial will ask you be done not by Takata they will hopefully supply the drug but the trial will actually be financed and run through the National Institute on Aging. And through collaboration that involves early Alzheimer's centers nationwide. So it will be an academic trial even though the drug is not a proprietary drug.
So all the people who are part of the National Institute on Aging will take part in doing their experiments at their particular hospitals around the country?
Dr. Gandy: Right. There are about forty Alzheimer's centers nationwide. And the infrastructure of testing new drugs that's run by the NIH is this network through this network of forty Alzheimer's centers. And so superimposed on that is the drug trials unit and so we work with them and that gives us access to the forty centers and anyone at the forty centers will have the opportunity to participate and we'll publicize the trials and they can you know contact folks at their local centers and be involved if they want to.
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