From time to time I tend to look at what is on the horizon as far as research for depression and or anxiety... usually I find a few things but just recently I have found a ton of new items and breakthroughs. I wanted to list them and see if anyone knows more about any of these, in hopes that we can all get some hope for the future. Most of these looked very promising to me and look like they have made some great discoveries that could soon aid people with depression! Do you know anything or know of any others?
List:
P7C3-A20
url: http://www.medicalne...cles/275841.php
It all came about when the research team decided to find out if ghrelin’s antidepressant effect could be enhanced with P7C3 compounds, which had been discovered previously to have neuroprotective properties.
What they learned is that P7C3 compounds did indeed enhance the antidepressant effect of ghrelin to a significant extent. They also found that a "highly active analog" of the P7C3-A20 compounds stimulated the creation of new neurons to a much greater extent than current antidepressant drugs on the market.
The results of the study indicate that the P7C3 compounds could help those suffering with depression associated with prolonged stress, as well as those who are obese or anorexic due to having altered ghrelin levels or ghrelin resistance.
NSI-189
Ok there is a great post on the loungcity forums about this one some people did a group buy and used it.... it looks very promising.... might want to skip to page 20 or so it is very long.
http://www.longecity.../58442-nsi-189/
NSA-189 is a proprietary new chemical entity that stimulates new neuron growth in the hippocampus, an area of the brain believed to be contributory in MDD and other conditions, such as Alzheimer’s disease and Post-traumatic stress disorder (PTSD). Phase 1b of the clinical trial is to test the safety and tolerability of the drug in depressed patients.
Karl Johe, PhD, Chief Scientific Officer and Chairman of Neuralstem’s Board of Directors, said, “We are pleased to be approved to begin testing NSI-189 in patients who suffer from depression. Loss of hippocampal volume is a known characteristic in depressed patients. NSI-189 stimulates neurogenesis and increases hippocampal volume in healthy adult mice, at the same time reversing behavioural symptoms in mouse depression models, so it could address depression at the source.”
Maurizio Fava, MD, Slater Family Professor of Psychiatry at Harvard Medical School and Executive Vice Chair of the Department of Psychiatry at Massachusetts General Hospital, is a leading researcher into MDD and helped to design the Neuralstem trial, added, “It is exciting to see a new class of drugs that potentially offers a novel and different approach to this disease moving into patients.”
Neuralstem’s technology enabled the creation of neural stem cell lines from areas of the human CNS, including the hippocampus, a part of the brain involved in memory and the generation of new neurons. From this, Neuralstem has created virtually unlimited amounts of mature human neurons and glia in laboratory dishes which can be used to mimic the natural brain environment to test the drug’s effects.
NSI-189 is the lead compound in Neuralstem’s neuroregenerative small molecule drug platform, which the company plans to develop into orally administered drugs for MDD and other psychiatric disorders, such as anxiety, bipolar disorder, PTSD and Alzheimer’s disease. In previous tests, NSI-189 significantly improved behavioural responses associated with depression. In humans, it may reverse the human hippocampal atrophy seen in MDD and other disorders, reversing their symptoms.
The NSI-189/MDD trial is a double-blind, randomised, placebo-controlled, multiple-dose escalating trial evaluating the safety, tolerability, pharmacokinetics and pharmacodynamic effect of NSI-189 in the treatment of MDD. Phase 1a tested escalating doses of single administration in healthy patients. Phase 1b will test the safety of escalating doses for 28 daily administrations in 24 depressed patients, and will take approximately 6 months to complete.
GSK650394
In a nutshell, they found SGK1 was able to prolong the negative aspects of stress hormones. By keeping the GR active even
after the cortisol had left the cells, the SGK1 protein got in the way of the long-term “good” the cortisol had done. It
inhibited neurogenesis.
Using animals models and depressive patient’s blood samples, the team used a pharmacological compound known as GSK650394
that obstructs SGK1 and discovered they were able to increase the growth of new brain cells.
Not only is this good news for those without MS, but also it is incredibly important for those that do.
Atrophy is an incredibly lousy affect for an MS patient and with depression and anger being so prevalent among patients
(in the United States alone, there are around 350,000 reported cases of MS with a mind numbing 75% or more with depression
and anger issues) combating this is extremely important.
Microglia-stimulating drugs
URL: http://new.huji.ac.il/en/article/18551
Now researchers at the Hebrew University of Jerusalem have shown that changes in one type of non-neuronal brain cells,
called microglia, underlie the depressive symptoms brought on by exposure to chronic stress. In experiments with animals,
the researchers were able to demonstrate that compounds that alter the functioning of microglia can serve as novel and
efficient antidepressant drugs.
The researchers mimicked chronic unpredictable stress in humans — a leading causes of depression — by exposing mice to
repeated, unpredictable stressful conditions over a period of 5 weeks. The mice developed behavioral and neurological
symptoms mirroring those seen in depressed humans, including a reduction in pleasurable activity and in social interaction,
as well as reduced generation of new brain cells (neurogenesis) — an important biological marker of depression.
The researchers found that during the first week of stress exposure, microglia cells undergo a phase of proliferation and
activation, reflected by increased size and production of specific inflammatory molecules, after which some microglia begin
to die. Following the 5 weeks of stress exposure, this phenomenon led to a reduction in the number of microglia, and to a
degenerated appearance of some microglia cells, particularly in a specific region of the brain involved in responding to
stress.
HDAC2 Inhibitor
Many times, mild to moderate depression does not respond to SSRI treatment alone. HDAC inhibitors, such as valproic acid, are currently used as mood stabilizers and anti-epileptics, but as a stand alone, valproic acide is not an effective treatment for depression. By effectively controlling the therapeutic dose of both drugs, and establishing a novel combination drug therapy strategy, more effective treatments for mild to moderate depression and other mood disorders can be developed. This combination treatment strategy will target the large population of people who have mild to moderate depression in which SSRIs are not particularly effective.
hedgehog pathway
url: http://chipur.com/ho...-at-the-source/
MI-4
The latest hope as a psychiatric rescue drug is called MI-4, and news of its promise was reported earlier this week at the
San Diego meeting of the Federation of American Societies for Experimental Biology (FASEB). Scientists also have
identified the drug as Ro-25-6981.
In the test tube, MI-4 was found to simultaneously increase the availability in the brain of three neurotransmitters that
play a key role in depression: serotonin, dopamine and norepinephrine. Researchers led by Jeffery N. Talbot of Roseman
University of Health Science in Henderson, Nev., found that in mice that had been stressed and trained to expect no rescue
from frightening circumstances -- a depression-like condition called "learned helplessness" -- MI-4 quickly restored more
hopeful behavior and continued to do so for three weeks -- a lengthy stretch for a mouse.
Compared with a placebo medication, MI-4 made virtual social butterflies of mice who had been brought low by social defeat,
and whose depression manifested as withdrawal. And for a continuous three-week period, it helped fortify those mice against
the soul-crushing effects of further social defeat.
MI-4 appears to have several advantages over ketamine, which, as a drug that induces a sort of out-of-body high when used at
higher doses and is, therefore, considered to have abuse potential. Mice taking MI-4 were no more likely to hang out close to
the drug-dispenser than they were to wander around and explore and socialize -- a clear sign that its abuse or addictive
potential is low.
ALKS-5461
URL: http://chipur.com/fe...-of-the-future/
ALKS 5461 is a proprietary investigational oral medicine for the treatment of MDD. ALKS 5461 has a novel mechanism of action in the treatment of depressive symptoms based on modulation of the opioid system in the brain, employing a balanced combination of agonist and antagonist components that act on opioid receptors, and includes a novel opioid modulator, samidorphan, discovered by Alkermes. Samidorphan was formerly referred to as ALKS 33. In October 2013, the FDA granted Fast Track status for ALKS 5461 for the adjunctive treatment of MDD in patients with an inadequate response to standard therapies.
GLYX-13
http://www.dddmag.com/news/2014/05/naurex%E2%80%99s-cns-drugs-hit-major-milestones
works like ketamine by modulating the NMDA receptor, and like ketamine it works immediately. Glutamate based drugs seem to be the future of psychiatric medications.
NRX-1074
The objectives of the Phase 2a study now underway for NRX-1074 are to evaluate the safety and efficacy of a single dose of the compound administered to subjects with MDD. NRX-1074 is considerably more potent than GLYX-13 and, in preclinical studies, it has shown activity similar to GLYX-13, including signs of rapid onset and long-acting duration of antidepressant-like effect. The Phase 2a study of NRX-1074 follows successful completion of a randomized, placebo-controlled Phase 1 study in which NRX-1074 was well-tolerated by normal volunteers. It is Basically a stronger version of GLYX-13 in pill form.
BOTOX
Tal Medical lfms
LFMS uses an external electromagnetic coil to apply a time-varying magnetic field to the brain, which induces an electrical field. LFMS uses electric fields that are vastly different from the existing neuromodulation technologies, electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS). The LFMS technology was licensed from McLean Hospital, a psychiatric research facility in Belmont, Ma.
Transcranial Pulsating Electro Magnetic Fields (T-PEMF)
In the latest trial, the results of which were published on April 15th in Acta Neuropsychiatrica, 65 patients burdened by
seemingly untreatable depression were given the helmets to use for a period of eight weeks (they also continued taking
their regular anti-depressant medication). 34 participants received a half hour dose of Transcranial Pulsating
Electromagnetic Fields (T-PEMF) once a day and 31 had two half hour doses. All participants used the helmet in their own
homes.
The device contains seven coils that deliver T-PEMF to brain tissues. The helmet’s principal architect, Professor Steen
Dissing from Copenhagen’s Faculty of Health Sciences, reveals that the device “mimics electrical fields in the brain which
trigger the body’s own healing mechanism.” The pulses activate cerebral capillaries that form new blood vessels as they
imitate the brain’s own electrical signalling.
At the end of the trial, the 34 people who received one dose a day showed a 73% improvement in their wellbeing; the 31
others who had two improved by 67%. The results surprised researchers who concluded that the biochemical process should
not be forced. "You cannot keep pulsing," says Professor Dissing. “The release of growth hormones, and their synthesis in
the capillaries, can only occur so fast. That's rate limiting,” he explains. Nevertheless, some participants felt the
positive effects after just a week.
The pulses are so minute that the patient cannot detect any sensation, and the only side effect so far is occasional nausea
that immediately disappears after treatment. The helmet also had the additional benefit of increasing patients’ tolerance
for anti-depression medications.
T-PEMF could ultimately replace controversial electroconvulsive therapy (ECT) for some sufferers, a treatment graphically
recalled in the writings of Sylvia Plath. It has been used for severe forms of depression since the 1940s.
Purmorphamine
CRF1 antagonist
Depression and anxiety disorders are highly prevalent forms of mental illness that are considered to be stress-related disorders because some form of stressful life event often triggers their symptoms. Corticotropin-releasing factor (CRF) is a 41-amino-acid neuropeptide involved in mediating neuroendocrine, autonomic and behavioural responses to stress, and clinical studies provide evidence for the role of CRF in the development of depression and anxiety disorders. Two CRF receptor subtypes have been identified to date - the CRF(1) receptor and the CRF(2) receptor. Preclinical models provide evidence of a role for CRF(1) receptors in the activation of the stress response. Data from these experiments suggest that antagonism of CRF(1) receptor activity may provide an effective pharmacological treatment for stress-related psychiatric disorders. This review highlights progress to date with the development of CRF(1) receptor antagonists as potential pharmacotherapies for depression and anxiety disorders. Although additional research is needed to fully investigate the efficacy and safety profiles of CRF(1) receptor antagonists as candidate medications for these disorders, the results of preclinical experiments and clinical trials are encouraging. Further development of these compounds is warranted.
mTORC1
url: http://www.newscient...ml#.U2wXLvldX4w
Duman thinks that REDD1 causes brain shrinkage by inhibiting the production of another protein called mTORC1. mTORC1 enables the production of a substance that brain cells use to repair themselves. Earlier work by the group showed that ketamine boosted the levels of mTORC1, providing one explanation for its antidepressant affects.
But if REDD1 is behind the reduction in mTORC1, targeting it directly could be a good treatment strategy, says Duman.
"Acute stress is a normal part of life, and you bounce back and that's fine," says Colleen Loo at the University of New South Wales in Sydney, Australia, who is studying ketamine as a treatment for depression. "But the longer you're depressed the more likely you are to have shrinkage in the brain. This study is teasing out what are the molecular pathways by which stress translates to shrinkage of brain cells."
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