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Dr. Bob is Robert Hsiung, MD,
[email protected]Shown: posts 1 to 19 of 19. This is the beginning of the thread.
Posted by SLS on November 21, 2010, at 6:44:48
A new paradigm, perhaps?
- Scott
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Neuralstem Files FDA Application for First Drug Therapy NSI-189 for the Treatment of Major DepressionROCKVILLE, Md., Nov. 17, 2010 /PRNewswire-FirstCall/ -- Neuralstem, Inc. (NYSE Amex: CUR) announced that it has filed an Investigational New Drug (IND) application with the United States Food and Drug Administration (FDA) to begin two Phase I safety trials to test NSI-189, its first small molecule compound, for the treatment of major depression. NSI-189 is a proprietary new chemical entity discovered by Neuralstem that stimulates new neuron growth in the hippocampus, an area of the brain that is believed to be involved in depression.
(Logo: http://photos.prnewswire.com/prnh/20061221/DCTH007LOGO )
(Logo: http://www.newscom.com/cgi-bin/prnh/20061221/DCTH007LOGO )
"This marks more than just a significant milestone for the company: we believe our compound represents the next generation of antidepressant treatment based on a new mechanism of action that may, for the first time, fundamentally modify the disease," said Neuralstem President & CEO Richard Garr. "NSI-189 also validates Neuralstem's proprietary neural stem cell screening approach as a source for discovering novel compounds that affect complex stem cell biology rather than a single molecular target."
"The antidepressants that are available today are based on the theory of serotonin deficiency," explained Karl Johe, PhD, Chief Scientific Officer and Chairman of Neuralstem's Board of Directors. "NSI-189 is based on a new theory that chronic exposure to stress hormones can inhibit the growth of new neurons in certain regions of the brain. This can lead to hippocampal atrophy and depression. We believe that this neurogenic approach to brain self-repair may be applicable in multiple diseases including: Alzheimer's disease, mild cognitive impairment, dementia, schizophrenia, cognitive complications from diabetes, post-traumatic stress syndrome and traumatic brain injury, all of which are indications that the company intends to pursue with this new class of drugs."
About NS-189: Stimulating Neurogenesis To Address Central Nervous System Conditions
NS-189 is the first in a class of compounds that Neuralstem plans to develop into orally administered drugs. These appear to have the effect of "recruiting" the patient's own neural stem cells to repair or protect against damage to the Central Nervous System (CNS) from disease or injury.
NSI-189 stimulated neurogenesis of human hippocampus-derived neural stem cells in- vitro. In mice, NSI-189 both stimulated neurogenesis of the hippocampus and increased its overall volume as well. Therefore, NSI-189 may reverse the human hippocampal atrophy seen in major depression and schizophrenia. This program has received significant support from both the Defense Advanced Research Projects Agency (DARPA) and the National Institutes of Health (NIH).
The Neuralstem small molecule platform results from discoveries made through Neuralstem's ability to generate stable human neural stem cell lines suitable for screening large chemical libraries. The platform complements Neuralstem's cell therapy platform, in which brain and spinal cord stem cells are transplanted directly into diseased areas to repair and/or replace diseased or dead cells.
About the Trial
Neuralstem has filed an IND with the FDA to conduct two Phase I safety trials. The first trial will involve normal healthy volunteers testing the safety of escalating doses of a single administration of NSI-189. The second trial is designed to test the safety of escalating doses of daily administration for 28 days in depressed patients. The entire trial is expected to be approximately one year in duration.
Further information will be available on the Neuralstem website after the FDA approves the trial.
About Neuralstem
Neuralstem's patented technology enables the ability to produce neural stem cells of the human brain and spinal cord in commercial quantities, and the ability to control the differentiation of these cells constitutively into mature, physiologically relevant human neurons and glia. Neuralstem is in a FDA-approved Phase I safety clinical trial for Amyotrophic Lateral Sclerosis (ALS), often referred to as Lou Gehrig's disease.
In addition to ALS, the company is also targeting major central nervous system diseases, including traumatic spinal cord injury, ischemic spastic paraplegia, and Huntington's disease. The company has also submitted an IND (Investigational New Drug) application to the FDA for a Phase I safety trial in chronic spinal cord injury.
Neuralstem also has the ability to generate stable human neural stem cell lines suitable for the systematic screening of large chemical libraries. Through this proprietary screening technology, Neuralstem has discovered and patented compounds that may stimulate the brain's capacity to generate new neurons, possibly reversing the pathologies of some central nervous system conditions. Neuralstem plans to initiate clinical trials with its lead compound to treat major depression and potentially other diseases, such as schizophrenia, Alzheimer's disease, traumatic brain injury, posttraumatic stress syndrome, and stroke.
For more information, please go to www.neuralstem.com.
Cautionary Statement Regarding Forward Looking Information
This news release may contain forward-looking statements made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such forward-looking statements in this press release regarding potential applications of Neuralstem's technologies constitute forward-looking statements that involve risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for future capital, dependence upon collaborators and maintenance of our intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect our results and other risks and uncertainties are detailed from time to time in Neuralstem's periodic reports, including the annual report on Form 10-K for the year ended December 31, 2009, and in its quarterly report on Form 10-Q for the period ended September 30, 2010.
Posted by Phillipa on November 21, 2010, at 9:52:42
In reply to New drug for depression - Long wait until approval, posted by SLS on November 21, 2010, at 6:44:48
Very long wait and sounds very expensive when and if the drug is approved as stem cells are expensive. Seems this med covers a lot of autoimmune diseases so I wonder if they are thinking MI is autoimmune as ALS I think is. And to cover so many degenerative illnesses and even Alzheimers I guess I won't exist when this med is approved. But for the younger folks this is great. Phillipa
Posted by linkadge on November 21, 2010, at 11:32:35
In reply to New drug for depression - Long wait until approval, posted by SLS on November 21, 2010, at 6:44:48
My personal thoughts are that purely neurotrophic agents are not going to routinely display antidepressant effects.
In the Flinders sensitive line (a breed of depressive rats) there is evidence of excessive hippocampal neurogenesis. Nortriptyline administration improves the behavioral deficits while *lowering* hippocampal neurogenesis.
Also, hippocampal volume loss is not present in all studies of depressed patients.
My thoughts are that this agent may be beneficial for a certain subgroup of depressed patients, or certain symptoms of depression, but not all.
Posted by Willful on November 21, 2010, at 14:07:26
In reply to New drug for depression - Long wait until approval, posted by SLS on November 21, 2010, at 6:44:48
The drug would stimulate growth of the body's own stem cells-- not use other stem cells to repair something in the body-- so it really has nothing to do with the uses of stem cells that are generally talked of.
It will probably be expensive-- because all new meds are expensive-- but not for any other reason.
Sounds pretty interesting to me. I don't see why the wait would be any longer than that for any investigational med-- ie you need different levels of testing and this is only at Phase I. So clearly it will be a while. Twenty years?? hardly..
if it works. I certainly would expect some new avenues and drugs for depression in the next years. Whether a neurogenic drug will be sufficient in and of itself I doubt. One would need new experiences, to learn new behavior, but that would be doable if the hippocampus is able to overcome the seeming suppression by stress hormones. I really hope this line of investigation bears some fruit.
Willful
Posted by Bob on November 21, 2010, at 14:45:54
In reply to New drug for depression - Long wait until approval, posted by SLS on November 21, 2010, at 6:44:48
I saw this too. Hopefully it represents a new and promising direction.
Posted by SLS on November 21, 2010, at 16:58:07
In reply to Re: New drug for depression - Long wait until approval, posted by linkadge on November 21, 2010, at 11:32:35
> My personal thoughts are that purely neurotrophic agents are not going to routinely display antidepressant effects.
Yes. I have my doubts. Perhaps the drug does other things.
I sometimes think that a decrease in the volume of hippocampal tissue seen in depression is an atrophy due to disuse, as depression probably reduces afferent activity upstream that would normally stimulate the hippocampus to function and remain healthy.
It is a bit of a conundrum.
- Scott
Posted by linkadge on November 21, 2010, at 18:05:44
In reply to Re: New drug for depression - Long wait until approval » linkadge, posted by SLS on November 21, 2010, at 16:58:07
>sometimes think that a decrease in the volume of >hippocampal tissue seen in depression is an >atrophy due to disuse,
Those are my thoughts exactly. Any drug that gets you out of bed and back to enjoying a range of life's challenges and rewards will undoubtly have a very favorable impact on brain function.
Linkadge
Posted by linkadge on November 21, 2010, at 18:08:01
In reply to Re: New drug for depression - Long wait until approval » linkadge, posted by SLS on November 21, 2010, at 16:58:07
Its just like there's probably some correlation between depression and bone / muscle mass loss.
Does this mean any drug that promotes bone or muscle formation will act as an antidepressant?
No, but an effective antidepressant might help reverse bone / muscle mass loss due to depression.
Linkadge
Posted by Bob on November 21, 2010, at 18:12:08
In reply to Re: New drug for depression - Long wait until approval » SLS, posted by linkadge on November 21, 2010, at 18:08:01
Is the possibility of this compound being an antidepressant based on anything other than the claim that it induces neural repair? Did they do a forced swim test, or anything else?
Posted by Phillipa on November 21, 2010, at 19:12:12
In reply to Re: New drug for depression - Long wait until approval » SLS, posted by linkadge on November 21, 2010, at 18:08:01
I feel you speak with much more knowledge than I but I've read that SSRI's do contribute to bone loss but didn't know about muscle. How are they related? I don't get it? Phillipa
Posted by linkadge on November 21, 2010, at 19:44:03
In reply to Re: New drug for depression - Long wait until approval » linkadge, posted by Bob on November 21, 2010, at 18:12:08
Good question, I don't know.
Posted by bleauberry on November 22, 2010, at 5:59:49
In reply to New drug for depression - Long wait until approval, posted by SLS on November 21, 2010, at 6:44:48
I don't think neuron growth is going to be a big player in advancing treatment success in depression. It, like serotonin deficiency theory, is too limited in scope. Depression is more wide ranging than either of those simplistic views.
What strikes me odd is how they claim stress hormones cause the problems that lead to depression and this medicine repairs the damage.....yet not a thought to....how about let's deal with those stress hormones? Duh?
Posted by SLS on November 22, 2010, at 6:47:37
In reply to Re: New drug for depression - Long wait until approval, posted by bleauberry on November 22, 2010, at 5:59:49
> What strikes me odd is how they claim stress hormones cause the problems that lead to depression and this medicine repairs the damage.....yet not a thought to....how about let's deal with those stress hormones? Duh?
Well, in drug development, we have different strategies to synthesize and identify candidates for therapeutic compounds. With psychiatric drugs, there are paradigms that screen for psychotropic drugs that involve little more than trial-and-error with rats. The synthesis of designer drugs based upon theoretical mechanisms of action often results in failure because so little is understood about the etiology of affective disorders. So, drugs are screened empirically using behavioral indexes. The reason I mention all of this is that it is very likely that this new compound has shown antidepressant activity using empirical paradigms that have been established as effective for identifying antidepressant drugs. In other words, any reference to the mechanisms of action of the new drug is really just an educated guess based upon the various theories currently being suggested.
- Scott
Posted by linkadge on November 22, 2010, at 6:53:21
In reply to Re: New drug for depression - Long wait until approval » bleauberry, posted by SLS on November 22, 2010, at 6:47:37
I remember when they were saying that the cortisol modulating drug RU-486 was being 'fast tracked' for psychotic depression. This was about 12 years ago.
Linkadge
Posted by SLS on November 22, 2010, at 7:13:17
In reply to Re: New drug for depression - Long wait until approval, posted by linkadge on November 22, 2010, at 6:53:21
> I remember when they were saying that the cortisol modulating drug RU-486 was being 'fast tracked' for psychotic depression. This was about 12 years ago.
Been there, done that. RU-486 (mifepristone) did not affect me any therapeutic way. However, after the full 8 days of treatment as recommended in the treatment protocol, I felt "washed-out". The adrenals were probably exhausted.
Alan Shatzberg was the leading investigator proposing mifeptistone as a treatment for psychotic depression. I corresponded with him as well as a European investigator whose name I don't remember off hand. After all was said and done, it seems that mifepristone can reduce the psychotic symptoms of psychotic depression without resolving the depression itself.
I guess the drug was fast-tracked, but ultimately failed to demonstrate efficacy in the accelerated schedule of studies.
- Scott
Posted by SLS on November 22, 2010, at 7:28:43
In reply to Re: New drug for depression - Long wait until approval, posted by SLS on November 22, 2010, at 7:13:55
Sorry. I was wrong.
> I felt "washed-out". The adrenals were probably exhausted.
It is not that the adrenals would be exhausted so much as they would simply be turned-off as the result of a negative feedback loop.
- Scott
Posted by linkadge on November 22, 2010, at 8:20:37
In reply to Re: New drug for depression - Long wait until approval, posted by SLS on November 22, 2010, at 7:28:43
I think the opposite might be true for some people. That is, depression causes stress. I think stress can mask depression. The first time I got depressed, I do remember initially (for the first few months) feeling blah, miserable, apathetic etc. After that (as I was falling behind in responsiabilities), the anxiety began to kick in, perhaps as an adaptive mechanism (i.e. if you can't find positive motivation to do the things you need to do, I'm going to use negative motivation i.e. anxiety, to get you to do the things you need to do). But it didn't start with anxiety or insomnia. Those symptoms came after the depression got more severe.
Some people only have the motivation to do things when they are under stress. For these people, its as if the brain circuts involved in taking pleasure in being proactive are not functioning well. As a result, a more reactive, coping strategy is used.
Linkadge
Posted by Phillipa on November 22, 2010, at 19:04:26
In reply to Re: New drug for depression - Long wait until approval, posted by linkadge on November 22, 2010, at 8:20:37
Maybe for some but not for me as was healthy as a horse felt great high energy then wham first panic attack out of nowhere. So for me it's always been anxiety. Phillipa
Posted by FluffMama on November 28, 2010, at 23:53:58
In reply to New drug for depression - Long wait until approval, posted by SLS on November 21, 2010, at 6:44:48
This is cool - at least we can see that different theories are being tested and new types of drugs are coming our way. ;) I find things like this very encouraging. Sure it might not work. But what if it DOES? It might take a long time. But what if it DOESN'T? Maybe I'm naive, but I'd rather be hopeful for months and then disappointed than be hopeless for months and then continue that way . . .
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