![[dr. bob]](/dr-bob-sm.gif)
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by wendy b. on July 30, 2003, at 9:58:39
The following is copyright New York Times. I appended the whole article, in case you don't have an account with the Times. It's free, but you do have to sign up (I think it's worth it, don't have to buy the paper!)
Hope this interests somebody out there, especially people like me with memory problems.
best,
Wendy
***********
July 29, 2003Race Is On for a Pill to Save the Memory
By DAVID TULLERThey are called smart pills or brain boosters or, to use the preferred pharmaceutical term, cognitive enhancers.
But whatever the name given to compounds created to prevent or treat memory loss, drug companies and supplement producers — eager to meet the demands of a rapidly growing market — are scrambling to exploit what they view as an enormous medical and economic opportunity.
Three drugs being prescribed for Alzheimer's disease — donepezil (Aricept), galantamine (Reminyl) and rivastigmine (Exelon) — have been shown to delay somewhat the loss of mental abilities in people with the illness. So has the drug memantine, which has been used for years in Europe but has not been approved in the United States. Some experts also say that performing mental exercises and adding fish oil to the diet can delay memory decline.
Pharmaceutical companies are investigating dozens of other compounds to see whether they can help people who have memory difficulties but have not progressed to Alzheimer's. Some researchers hope that drugs will eventually prevent the deficits that even healthy elderly people experience.
Much of the excitement among pharmaceutical companies, which have dozens of drugs in development, stems from advances in clarifying some of the brain processes and biochemical pathways that can hinder or help memory storage and retrieval, said Dr. Paul R. Solomon, a professor of psychology at Williams College.
"The basic research into the causes of memory disorders is going very rapidly," said Dr. Solomon, who is also co-director of the Memory Clinic at the Southwestern Vermont Medical Center in Bennington.
But it will probably be at least five years before any of those drugs meet the standards for approval by the Food and Drug Administration, researchers said.
Clearly, the market for memory enhancers is growing with the aging of the population.
Dr. Steven T. DeKosky, a professor of neurology and psychiatry at the University of Pittsburgh School of Medicine, says he has noticed a marked increase in anxiety among baby boomers, who are watching their parents descend into Alzheimer's and hoping that new medicines will help them avoid the same fate.
"People in their 40's and 50's are saying: `How can you help my mother? And, by the way, how can I avoid this?' " Dr. DeKosky said. "Ten years ago, people wanted to know how frequently they should have their blood pressure checked and what sorts of food they should eat. Nobody ever asked what they should be doing to prevent themselves from getting a late-life dementia."
Even among those who are already suffering memory loss, Alzheimer's is far from the only source. An estimated four million Americans have it, but millions more suffer from other disorders that can lead to dementia, including Parkinson's disease, multiple sclerosis, stroke, head trauma and schizophrenia.
Experts estimate that an additional four million people have a syndrome called mild cognitive impairment, which may progress to Alzheimer's. People with the impairment can function on their own but have gaps in their memories.
Economic imperatives are also driving the search for new and better treatments for memory disorders.
The current cost of Alzheimer's alone runs $100 billion or more, said Dr. William Thies, vice president for medical and scientific affairs of the Alzheimer's Association, a research and support group.
If no new medications for memory disorders are found, Dr. Thies added, the number of Alzheimer's patients could quadruple by midcentury.
"That's going to bankrupt our health care system," he said. "So there's a need to find a way to short-circuit that impending disaster."
Except for extreme cases like advanced Alzheimer's, memory disorders do not generally disrupt what is often called procedural memory, the ability to perform basic tasks or motor skills like riding a bicycle or getting dressed.
Far more vulnerable is episodic memory, the ability to recall specific information about people, dates and events. Many of the new compounds being scrutinized seek to improve the way recent memories are stored, transformed into long-term memories and brought back into consciousness when needed.
Drugs approved specifically for Alzheimer's are being tested in patients who have mild cognitive impairment. But the medications can have side effects like nausea and diarrhea. So researchers are looking ahead to the second generation of memory enhancers, some of them now in clinical trials.
Some of the drug companies most involved in the search are small enterprises, focused on specific pathways or aspects of brain biochemistry. Memory Pharmaceuticals in Montvale, N.J., is developing compounds that maintain brain levels of a substance called cyclic AMP, which transmits intracellular signals and has been shown in mice to play a role in memory formation and retrieval.
Another company, Cortex Pharmaceuticals in Irvine, Calif., has two drugs in clinical trials that bind themselves to sites on nerve cells called AMPA receptors. The receptors respond to signals between cells carried by the neurotransmitter glutamate, and the drugs, called ampakines, are intended to enhance the strength of the incoming signal.
"It's like an amplifier to a stereo set, and you can turn up the volume of brain activity quite a bit by using these compounds," said Dr. Roger Stoll, president, chief executive and chairman of Cortex.
Despite optimism among neuroscientists about eventual success, few expect memory enhancers to be a panacea. Many researchers acknowledge that even if they find effective treatments, there is no guarantee that the drugs will do anything for people who age normally.
There is even less optimism that these drugs will boost the brain power of younger people hoping to master a foreign language or excel on a calculus examination.
Although some drugs have clearly enhanced the ability of animals to learn and perform routine tasks, that does not necessarily mean the same medications will help people remember names and faces, said Dr. Rodney Pearlman, president and chief executive of Saegis Pharmaceuticals in Half Moon Bay, Calif.
"It isn't clear that animals use the same kinds of memories that humans do," said Dr. Pearlman, whose company is developing several memory enhancers. "A mouse doesn't have to remember a PIN number to get along during the day."
Posted by jrbecker on July 30, 2003, at 13:02:56
In reply to Race is on for Pill to Save Memory, fr. NYTimes, posted by wendy b. on July 30, 2003, at 9:58:39
what they fail to mention in this article is that both these drugs (and similar lines of compounds in development from these companies) are being tested for mood disorders. Memory Pharm's program concentrates on PDE4 inhibitors, which helps to increase cAMP, and thus (brain-derived neurotrphic factor) BDNF in the brain. Cortex's research focuses on AMPAkines, a line of compounds thought to have a therapeutic role in a variety of psychiarric illnesses, including Alzheimer's, Schizophrenia, and mood disorders, via BDNF and other neuroprotective actions.
Both of these lines of drug research underscore the theory of neural degeneration/neural plasticity that might [partially or more fully explain] the underlying causes behind some psychiatric disorders.
> The following is copyright New York Times. I appended the whole article, in case you don't have an account with the Times. It's free, but you do have to sign up (I think it's worth it, don't have to buy the paper!)
>
> Hope this interests somebody out there, especially people like me with memory problems.
>
> best,
> Wendy
>
>
> ***********
> July 29, 2003
>
> Race Is On for a Pill to Save the Memory
> By DAVID TULLER
>
> They are called smart pills or brain boosters or, to use the preferred pharmaceutical term, cognitive enhancers.
>
> But whatever the name given to compounds created to prevent or treat memory loss, drug companies and supplement producers — eager to meet the demands of a rapidly growing market — are scrambling to exploit what they view as an enormous medical and economic opportunity.
>
> Three drugs being prescribed for Alzheimer's disease — donepezil (Aricept), galantamine (Reminyl) and rivastigmine (Exelon) — have been shown to delay somewhat the loss of mental abilities in people with the illness. So has the drug memantine, which has been used for years in Europe but has not been approved in the United States. Some experts also say that performing mental exercises and adding fish oil to the diet can delay memory decline.
>
> Pharmaceutical companies are investigating dozens of other compounds to see whether they can help people who have memory difficulties but have not progressed to Alzheimer's. Some researchers hope that drugs will eventually prevent the deficits that even healthy elderly people experience.
>
> Much of the excitement among pharmaceutical companies, which have dozens of drugs in development, stems from advances in clarifying some of the brain processes and biochemical pathways that can hinder or help memory storage and retrieval, said Dr. Paul R. Solomon, a professor of psychology at Williams College.
>
> "The basic research into the causes of memory disorders is going very rapidly," said Dr. Solomon, who is also co-director of the Memory Clinic at the Southwestern Vermont Medical Center in Bennington.
>
> But it will probably be at least five years before any of those drugs meet the standards for approval by the Food and Drug Administration, researchers said.
>
> Clearly, the market for memory enhancers is growing with the aging of the population.
>
> Dr. Steven T. DeKosky, a professor of neurology and psychiatry at the University of Pittsburgh School of Medicine, says he has noticed a marked increase in anxiety among baby boomers, who are watching their parents descend into Alzheimer's and hoping that new medicines will help them avoid the same fate.
>
> "People in their 40's and 50's are saying: `How can you help my mother? And, by the way, how can I avoid this?' " Dr. DeKosky said. "Ten years ago, people wanted to know how frequently they should have their blood pressure checked and what sorts of food they should eat. Nobody ever asked what they should be doing to prevent themselves from getting a late-life dementia."
>
> Even among those who are already suffering memory loss, Alzheimer's is far from the only source. An estimated four million Americans have it, but millions more suffer from other disorders that can lead to dementia, including Parkinson's disease, multiple sclerosis, stroke, head trauma and schizophrenia.
>
> Experts estimate that an additional four million people have a syndrome called mild cognitive impairment, which may progress to Alzheimer's. People with the impairment can function on their own but have gaps in their memories.
>
> Economic imperatives are also driving the search for new and better treatments for memory disorders.
>
> The current cost of Alzheimer's alone runs $100 billion or more, said Dr. William Thies, vice president for medical and scientific affairs of the Alzheimer's Association, a research and support group.
>
> If no new medications for memory disorders are found, Dr. Thies added, the number of Alzheimer's patients could quadruple by midcentury.
>
> "That's going to bankrupt our health care system," he said. "So there's a need to find a way to short-circuit that impending disaster."
>
> Except for extreme cases like advanced Alzheimer's, memory disorders do not generally disrupt what is often called procedural memory, the ability to perform basic tasks or motor skills like riding a bicycle or getting dressed.
>
> Far more vulnerable is episodic memory, the ability to recall specific information about people, dates and events. Many of the new compounds being scrutinized seek to improve the way recent memories are stored, transformed into long-term memories and brought back into consciousness when needed.
>
> Drugs approved specifically for Alzheimer's are being tested in patients who have mild cognitive impairment. But the medications can have side effects like nausea and diarrhea. So researchers are looking ahead to the second generation of memory enhancers, some of them now in clinical trials.
>
> Some of the drug companies most involved in the search are small enterprises, focused on specific pathways or aspects of brain biochemistry. Memory Pharmaceuticals in Montvale, N.J., is developing compounds that maintain brain levels of a substance called cyclic AMP, which transmits intracellular signals and has been shown in mice to play a role in memory formation and retrieval.
>
> Another company, Cortex Pharmaceuticals in Irvine, Calif., has two drugs in clinical trials that bind themselves to sites on nerve cells called AMPA receptors. The receptors respond to signals between cells carried by the neurotransmitter glutamate, and the drugs, called ampakines, are intended to enhance the strength of the incoming signal.
>
> "It's like an amplifier to a stereo set, and you can turn up the volume of brain activity quite a bit by using these compounds," said Dr. Roger Stoll, president, chief executive and chairman of Cortex.
>
> Despite optimism among neuroscientists about eventual success, few expect memory enhancers to be a panacea. Many researchers acknowledge that even if they find effective treatments, there is no guarantee that the drugs will do anything for people who age normally.
>
> There is even less optimism that these drugs will boost the brain power of younger people hoping to master a foreign language or excel on a calculus examination.
>
> Although some drugs have clearly enhanced the ability of animals to learn and perform routine tasks, that does not necessarily mean the same medications will help people remember names and faces, said Dr. Rodney Pearlman, president and chief executive of Saegis Pharmaceuticals in Half Moon Bay, Calif.
>
> "It isn't clear that animals use the same kinds of memories that humans do," said Dr. Pearlman, whose company is developing several memory enhancers. "A mouse doesn't have to remember a PIN number to get along during the day."
>
>
Posted by wendy b. on July 31, 2003, at 8:24:41
In reply to Re: Race is on for Pill to Save Memory, fr. NYTimes » wendy b., posted by jrbecker on July 30, 2003, at 13:02:56
> what they fail to mention in this article is that both these drugs (and similar lines of compounds in development from these companies) are being tested for mood disorders. Memory Pharm's program concentrates on PDE4 inhibitors, which helps to increase cAMP, and thus (brain-derived neurotrphic factor) BDNF in the brain. Cortex's research focuses on AMPAkines, a line of compounds thought to have a therapeutic role in a variety of psychiarric illnesses, including Alzheimer's, Schizophrenia, and mood disorders, via BDNF and other neuroprotective actions.
>Both of these lines of drug research underscore the theory of neural degeneration/neural plasticity that might [partially or more fully explain] the underlying causes behind some psychiatric disorders.
Dear JR,What are the PDE4, BNDF, and cAMP compounds, and what do they do? Can you refer me to any literature (not too techinical? Is that even possible?) on these? I am interested in the mood-stabilization aspect, and the neural degeneration/plasticity issues...
Also, I like to impress my pdoc, on occasion, with my vast stores of knowledge... He's very reluctant to experiment with my meds, and I get a little tired of it... Anyway, if you have any references that might be interesting on these compounds or related material, I'd be interested, maybe some others here, too.Thanks,
Wendy
Posted by jrbecker on July 31, 2003, at 14:44:19
In reply to Re: Race is on... » jrbecker, posted by wendy b. on July 31, 2003, at 8:24:41
> > what they fail to mention in this article is that both these drugs (and similar lines of compounds in development from these companies) are being tested for mood disorders. Memory Pharm's program concentrates on PDE4 inhibitors, which helps to increase cAMP, and thus (brain-derived neurotrphic factor) BDNF in the brain. Cortex's research focuses on AMPAkines, a line of compounds thought to have a therapeutic role in a variety of psychiarric illnesses, including Alzheimer's, Schizophrenia, and mood disorders, via BDNF and other neuroprotective actions.
>
> >Both of these lines of drug research underscore the theory of neural degeneration/neural plasticity that might [partially or more fully explain] the underlying causes behind some psychiatric disorders.
>
>
> Dear JR,
>
> What are the PDE4, BNDF, and cAMP compounds, and what do they do? Can you refer me to any literature (not too techinical? Is that even possible?) on these? I am interested in the mood-stabilization aspect, and the neural degeneration/plasticity issues...
> Also, I like to impress my pdoc, on occasion, with my vast stores of knowledge... He's very reluctant to experiment with my meds, and I get a little tired of it... Anyway, if you have any references that might be interesting on these compounds or related material, I'd be interested, maybe some others here, too.
>
> Thanks,
> WendyWendy,
There are really no trials on these meds yet for depression (they are in early phase trials for other conditions). It's certain that such studies will be surfacing soon in the next couple of years though -- if not for these particular compounds discussed in the above article, then for others like them. As you'll read more about in the links I've provided, all antidepressants as well as the mood stabilizers, lithium and depakote, protect against neurodegeneration, to varying degrees. In fact, the notion of this singular role that they all have in common is what makes many researchers contend why these drugs actually work. But remember, this is just one theory for the underlying cause(s) of depression and bipolar disorder. The real biological causes are most likely multivariant and differ for different people. But this is much closer to the real roots of it than believing it's just a matter of correcting serotonin and norepinephrine levels, etc.
Hopefully these links will provide some info, some are fairly straightforward summaries, and some are technical. Take your pick...
http://www.mcmanweb.com/article-234.htm
http://www.mcmanweb.com/article-191.htm
http://www.psycheducation.org/mechanism/BDNF.htm
http://www.future-drugs.com/admin/articlefile/ern020310.pdf
http://www.nature.com/cgi-taf/DynaPage.taf?file=/npp/journal/v22/n1/abs/1395408a.html
http://www.memorypharm.com/pipeline.html
http://www.medscape.com/viewarticle/439479_1
http://www.cortexpharm.com/html/news/01/01-30-01.html
Posted by wendy b. on August 1, 2003, at 8:17:09
In reply to Re: neurodegeneration, BDNF, cAMP, etc., posted by jrbecker on July 31, 2003, at 14:44:19
> Wendy,
>
> There are really no trials on these meds yet for depression (they are in early phase trials for other conditions). It's certain that such studies will be surfacing soon in the next couple of years though -- if not for these particular compounds discussed in the above article, then for others like them. As you'll read more about in the links I've provided, all antidepressants as well as the mood stabilizers, lithium and depakote, protect against neurodegeneration, to varying degrees. In fact, the notion of this singular role that they all have in common is what makes many researchers contend why these drugs actually work. But remember, this is just one theory for the underlying cause(s) of depression and bipolar disorder. The real biological causes are most likely multivariant and differ for different people. But this is much closer to the real roots of it than believing it's just a matter of correcting serotonin and norepinephrine levels, etc.
>
> Hopefully these links will provide some info, some are fairly straightforward summaries, and some are technical. Take your pick...Dear JR,
Wow, I'm amazed at the generosity you've shown here. And I appreciate very much the opportunity to read more on these topics - hope I can do something for you someday. What is your background (if you don't mind my asking)? Research, etc?
Again, many thanks... I may have a question or two for you after I do my homework!
Sincerely,
Wendy
Posted by zenhussy on August 1, 2003, at 9:17:10
In reply to Re: neurodegeneration, BDNF, cAMP, etc. » jrbecker, posted by wendy b. on August 1, 2003, at 8:17:09
begins?
I don't have time to read those links yet as I'm still dealing with the godchildren. I would love to get around to them this weekend though.
I've taken a formula years ago with cAMP and it was an effective part of my anti depressant cocktail (herbal vs. pharmaceutical) at that time.
Would either you or JR give me a holler when y'all get back to this discussion?
Many thanks.
And yes, it is ever so nice and surprising to see such generosity offered up so freely. = )
zenhussy
Posted by jrbecker on August 1, 2003, at 17:36:04
In reply to Re: neurodegeneration, BDNF, cAMP, etc. » jrbecker, posted by wendy b. on August 1, 2003, at 8:17:09
thanks, wendy. My background is partly psych/bio. And yes, I am in research!
> > Wendy,
> >
> > There are really no trials on these meds yet for depression (they are in early phase trials for other conditions). It's certain that such studies will be surfacing soon in the next couple of years though -- if not for these particular compounds discussed in the above article, then for others like them. As you'll read more about in the links I've provided, all antidepressants as well as the mood stabilizers, lithium and depakote, protect against neurodegeneration, to varying degrees. In fact, the notion of this singular role that they all have in common is what makes many researchers contend why these drugs actually work. But remember, this is just one theory for the underlying cause(s) of depression and bipolar disorder. The real biological causes are most likely multivariant and differ for different people. But this is much closer to the real roots of it than believing it's just a matter of correcting serotonin and norepinephrine levels, etc.
> >
> > Hopefully these links will provide some info, some are fairly straightforward summaries, and some are technical. Take your pick...
>
>
>
> Dear JR,
>
> Wow, I'm amazed at the generosity you've shown here. And I appreciate very much the opportunity to read more on these topics - hope I can do something for you someday. What is your background (if you don't mind my asking)? Research, etc?
>
> Again, many thanks... I may have a question or two for you after I do my homework!
>
> Sincerely,
>
> Wendy
Posted by SLS on August 1, 2003, at 19:51:53
In reply to Re: neurodegeneration, BDNF, cAMP, etc. » wendy b., posted by jrbecker on August 1, 2003, at 17:36:04
> thanks, wendy. My background is partly psych/bio. And yes, I am in research!
>
JRB, I'm glad you're on our side! Really.I imagine that you are too modest to accept this gracefully, but you are amazing. Thank you so much for your contribution here.
Sincerely,
Scott
Posted by zinya on August 2, 2003, at 13:13:43
In reply to Re: neurodegeneration, BDNF, cAMP, etc. » wendy b., posted by jrbecker on August 1, 2003, at 17:36:04
JRB,
greetings ... I've just stumbled on this thread from the link you gave to this from a newer thread today - I'll probably double-post this in both threads to hope to catch you.
I'm wondering if the experience I've been recounting to doctors who give me only glazed looks for the past 15 years could begin to be explained if I understand correctly the line of interconnection you seem to be outlining here between neural and (adrenal? and) depression-triggering 'damages'.
A brief history, as I know no other way to present my 'case study'. I lived 34 years with energy for anything I wanted, never knew what pain was really, not chronic pain. In 1981, after a serious roller skating accident which left me with a compression fracture between my 4th and 5th lumbars, i discovered a congenital anomaly (quite a unique one according to my chiropracter) involving an extra half a lumbar fused to my sacrum which has from birth presumably meant a pull on my right hip that creates something of an angle. Perhaps some childhood accidents like crashing on my coccix had some impact, but never chronic pain until that 1981 accident. It started first to manifest in sciatic pain for some years. Then a chronic viral infection beginning in 1985 entered the picture. By 1987, i crashed (compounded by the stress and grief of my father's death) into a 'black curtain' of zero energy and only at that point did the doctors look back and realize i'd been running with the chronic viral infection for 2 years, having gone in for sheer exhaustion, had blood tests but no one told me of the infection, figuring it would pass.
For two years from 87 to 89, recovery was elusive. Every time i would try to resume normal activity, which had included swimming between one and two miles a day prior to '87, i recrashed into zero energy even though i resumed with very gradual steps (like 1/4 mile only). Walking became a re-injuring activity. I was referred to various specialists who diagnosed Epstein-Barr, then Chronic Fatigue, also fibromyalgia, miofascial pain syndrome... I tried all kinds of traditional and nontraditional (eg acupuncture) methods.
I was given Prozac first in 89, later lithium (because of merely a one-day-ever manic episode and because i tend to do "fast talk" when i'm with a doctor trying to cram a lot into a visit and some then think i'm hyper but i'm not. What i've eventually come to realize is that my adrenal system, shown in blood work in 2000 to be depleted, is erratic but almost entirely on the no-adrenalin, no-energy side of the pendulum.
Okay, with that as some peripheral but converging background:
I've been telling my doctors for all these years that, in my lay terms, "My back goes out on me and then i just cascade downwards into no energy and feeling depressed." By which i mean that the nerve damage (pinched nerve) in my sacroiliac area -- or then also after getting hit in 1990 by a red-light-runner and suffering additional neck nerve damage from a concussion into my driver's window -- also enough nerve damage that i can no longer applaud as that hand clapping triggers nerve damage that also cycles into body-wide energy flagging and other downturns.
Doctors have been hard pressed to see how or why a reinjury to lower back nerve pain should be related to body-wide energy levels and depressive states. They seem to distrust me that i'm accurately assessing that i'm fine until a reinjury of my back and that that then alone launches a downcycle impacting depression.
Would an upshot of this research you have presented suggest that in fact there would be a plausible cause-effect linkage?
And, to get to remedies, as I'm now on Effexor (month 2 at 150 mg) after having tried without success Prozac, lithium, depakote, zoloft, paxil and celexa at various crisis moments over the past 15 years, usually having to quit due to side effects but sometimes because of no positive effect.
I have begun to wonder (since the Effexor I'd been led to hope would start to work on my adrenal system and show energy benefits by 150 mg levels but so far after 2 weeks at this level has shown none -- and i have had two back reinjuries -- rotated lumbar -- during this time period):
Would I perhaps be better off treating back injuries with stronger painkillers (I tend to try to get by with just 1/2 a vicodin which often is enough to be satisfactory but i've also learned that a full vicodin not only masks the pain but gives me actual energy restoration -- yet i am reluctant to take a full vicodin on a regular basis for fear of addiction), that perhaps if i did let myself take a full vicodin more immediately more regularly at the first sign of back pain, would i perhaps "envelop" the pain that perhaps then would not deplete (?) the adrenal system which then might not -- along the lines of what i gather from the research you cite -- trigger the depressive cycles??
I realize this can at best be answered on a theroretical level here based on a streamlined (!! believe me, you got the short version!) case study and no physical examination plus you are a researcher not a doctor. However, if you have any thoughts on the "logic" of the kind of connection I have long sensed intuitively lies at the root of this past 15 years of debilitation which has impacted my career and my ability to travel as i used to, etc. It's this lay sense that "my back (nerve damage in lumbar/sacrum) that goes out and then i cascade into depression that takes longer to recover from than the back pain itself."
Any thoughts? And apologies if this feels like an imposition in terms of being something out of your bailiwick.
thanks,
zinya
This is the end of the thread.
Psycho-Babble Medication | Extras | FAQ
Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.org
Script revised: February 4, 2008
URL: http://www.dr-bob.org/cgi-bin/pb/mget.pl
Copyright 2006-17 Robert Hsiung.
Owned and operated by Dr. Bob LLC and not the University of Chicago.