Anyone know more on this? Sounds like a cure to me
 

It has been approved for diabetes for a couple of years, so your doc could prescribe it tomorrow.



1: J Neurol Sci. 2008 Aug 15;271(1-2):131-6. Epub 2008 May 27.

The CRF-like peptide urocortin produces a long-lasting recovery in rats made
hemiparkinsonian by 6-hydroxydopamine or lipopolysaccharide.

Abuirmeileh A, Harkavyi A, Kingsbury A, Lever R, Whitton PS.

Department of Pharmacology, The School of Pharmacy, 29-39 Brunswick Square,
London WC1N 1AX, UK.

We have recently observed that the corticotropin releasing factor related peptide
urocortin (UCN) reverses key features of nigrostriatal neurodegeneration
following intracerebral injection of either 6-hydroxydopamine (6-OHDA) or
lipopolysaccharide (LPS). To determine the potential therapeutic utility of UCN
here we have studied whether these effects are sustained for several weeks
following peptide injection. In addition we have studied whether UCN still shows
efficacy in rats with more pronounced nigrostriatal lesions. Rats were lesioned
using 6-OHDA or LPS and injected with UCN either 7 or 14 days later. At different
time points animals were tested for rotational behaviour (apomorphine, 0.5 mg/kg)
and subsequently implanted with bilateral dialysis probes into the striata. The
following day rats were dialysed to estimate extracellular striatal dopamine (DA)
and then sacrificed for estimation of striatal tissue DA and subsequent
immunohistochemistry of TH(+) cells in the substantia nigra (SN). Toxin treated
rats given UCN 7 days later showed clear evidence of reduced nigrostriatal damage
both 28 and 84 days following UCN compared with saline injection. In rats given
UCN 14 days after toxin injection, by which time deficits were maximal, a
restoration of nigrostriatal damage was observed. This suggests that UCN is able
to elicit a sustained restoration of functional nigrostriatal integrity and has
the ability to produce a recovery in severely lesioned rats. These findings
suggest that stimulation of CRF (probably CRF(1)) receptors could have
therapeutic utility in PD.


PMID: 18508084 [PubMed - in process]

what?
 

can someone do a rough translation? Sounds like someone has tripped over a piece of potentially life altering information...but I cannot tell for sure. If so, it could get buried in a hurry by those who would prefer it not further undermine the american economy, heal the sick or raise the dead. A job for the NT research team....not me, I'm strictly a philosopher/cheerleader type with a rather jaded outlook.

I'll be watching this thread to see what happens next.

more data
 

1: J Neuroinflammation. 2007 Jul 21;4:19.

Urocortin, a CRF-like peptide, restores key indicators of damage in the
substantia nigra in a neuroinflammatory model of Parkinson's disease.

Abuirmeileh A, Harkavyi A, Lever R, Biggs CS, Whitton PS.

Department of Pharmacology, The School of Pharmacy, London, UK.
amjad.abuirmeileh@pharmacy.ac.uk <amjad.abuirmeileh@pharmacy.ac.uk>

We have recently observed that the corticotrophin releasing hormone (CRF) related
peptide urocortin (UCN) reverses key features of nigrostriatal damage in the
hemiparkinsonian 6-hydroxydopamine lesioned rat. Here we have studied whether
similar effects are also evident in the lipopolysaccaride (LPS) neuroinflammatory
paradigm of Parkinson's disease (PD). To do this we have measured restoration of
normal motor behaviour, retention of nigral dopamine (DA) and also tyrosine
hydroxylase (TH) activity. Fourteen days following intranigral injections of LPS
and UCN, rats showed only modest circling after DA receptor stimulation with
apomorphine, in contrast to those given LPS and vehicle where circling was
pronounced. In separate experiments, rats received UCN seven days following LPS,
and here apomorphine challenge caused near identical circling intensity to those
that received LPS and UCN concomitantly. In a similar and consistent manner with
the preservation of motor function, UCN 'protected' the nigra from both DA
depletion and loss of TH activity, indicating preservation of DA cells. The
effects of UCN were antagonised by the non-selective CRF receptor antagonist
alpha-helical CRF and were not replicated by the selective CRF2 ligand UCN III.
This suggests that UCN is acting via CRF1 receptors, which have been shown to be
anti-inflammatory in the periphery. Our data therefore indicate that UCN is
capable of maintaining adequate nigrostriatal function in vivo, via CRF1
receptors following a neuro-inflammatory challenge. This has potential
therapeutic implications in PD.

PMCID: PMC1976313
PMID: 17659087 [PubMed - indexed for MEDLINE]

1: J Neurosci Res. 2008 Feb 1;86(2):326-38.

Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the
adult rodent brain and induces recovery in an animal model of Parkinson's
disease.

Bertilsson G, Patrone C, Zachrisson O, Andersson A, Dannaeus K, Heidrich J,
Kortesmaa J, Mercer A, Nielsen E, Rönnholm H, Wikström L.

NeuroNova AB, Stockholm, Sweden.

We investigated the effects of exendin-4 on neural stem/progenitor cells in the
subventricular zone of the adult rodent brain and its functional effects in an
animal model of Parkinson's disease. Our results showed expression of GLP-1
receptor mRNA or protein in the subventricular zone and cultured neural
stem/progenitor cells isolated from this region. In vitro, exendin-4 increased
the number of neural stem/progenitor cells, and the number of cells expressing
the neuronal markers microtubule-associated protein 2, beta-III-tubulin, and
neuron-specific enolase. When exendin-4 was given intraperitoneally to naïve
rodents together with bromodeoxyuridine, a marker for DNA synthesis, both the
number of bromodeoxyuridine-positive cells and the number of neuronal precursor
cells expressing doublecortin were increased. Exendin-4 was tested in the
6-hydroxydopamine model of Parkinson's disease to investigate its possible
functional effects in an animal model with neuronal loss. After unilateral lesion
and a 5-week stabilization period, the rats were treated for 3 weeks with
exendin-4. We found a reduction of amphetamine-induced rotations in animals
receiving exendin-4 that persisted for several weeks after drug administration
had been terminated. Histological analysis showed that exendin-4 significantly
increased the number of both tyrosine hydroxylase- and vesicular monoamine
transporter 2-positive neurons in the substantia nigra. In conclusion, our
results show that exendin-4 is able to promote adult neurogenesis in vitro and in
vivo, normalize dopamine imbalance, and increase the number of cells positive for
markers of dopaminergic neurons in the substantia nigra in a model of Parkinson's
disease. (c) 2007 Wiley-Liss, Inc.


PMID: 17803225 [PubMed - indexed for MEDLINE]

1: J Neuroinflammation. 2008 May 21;5:19.

Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct
rodent models of Parkinson's disease.

Harkavyi A, Abuirmeileh A, Lever R, Kingsbury AE, Biggs CS, Whitton PS.

Department of Pharmacology, The School of Pharmacy, 29-39 Brunswick Square,
London WC1N 1AX, UK. alexander.harkavyi@pharmacy.ac.uk

BACKGROUND: It has recently become apparent that neuroinflammation may play a
significant role in Parkinson's disease (PD). This is also the case in animal
paradigms of the disease. The potential neuroprotective action of the
glucagon-like peptide 1 receptor (GLP-1R) agonist exendin-4 (EX-4), which is
protective against cytokine mediated apoptosis and may stimulate neurogenesis,
was investigated In paradigms of PD. METHODS: Two rodent 'models' of PD,
6-hydroxydopamine (6-OHDA) and lipopolysaccaride (LPS), were used to test the
effects of EX-4. Rats were then investigated in vivo and ex vivo with a wide
range of behavioural, neurochemical and histological tests to measure integrity
of the nigrostriatal system. RESULTS: EX-4 (0.1 and 0.5 mug/kg) was given seven
days after intracerebral toxin injection. Seven days later circling behaviour was
measured following apomorphine challenge. Circling was significantly lower in
rats given EX-4 at both doses compared to animals given 6-OHDA/LPS and vehicle.
Consistent with these observations, striatal tissue DA concentrations were
markedly higher in 6-OHDA/LPS + EX-4 treated rats versus 6-OHDA/LPS + vehicle
groups, whilst assay of L-DOPA production by tyrosine hydroxylase was greatly
reduced in the striata of 6-OHDA/LPS + vehicle rats, but this was not the case in
rats co-administered EX-4. Furthermore nigral TH staining recorded in 6-OHDA/LPS
+ vehicle treated animals was markedly lower than in sham-operated or EX-4
treated rats. Finally, EX-4 clearly reversed the loss of extracellular DA in the
striata of toxin lesioned freely moving rats. CONCLUSION: The apparent ability of
EX-4 to arrest progression of, or even reverse nigral lesions once established,
suggests that pharmacological manipulation of the GLP-1 receptor system could
have substantial therapeutic utility in PD. Critically, in contrast to other
peptide agents that have been demonstrated to possess neuroprotective properties
in pre-clinical models of PD, EX-4 is in current clinical use in the management
of type-II diabetes and freely crosses the blood brain barrier; hence, assessment
of the clinical efficacy of EX-4 in patients with PD could be pursued without
delay.

PMCID: PMC2426681
PMID: 18492290 [PubMed - indexed for MEDLINE]

now, to review
 

I'm still trying to get my mind around this one but I do know-
1) All these and about three more are less than two years old, lot of older diabetes stuff but not PD
2) At least two teams after it with Whitton's in the lead
3) Whitton seems to do good work and has been around awhile, he has written the best review of my favorite hypothesis (bacterial toxins) that I've seen and I know enough on that one to know that he is one sharp fellow. He is not the type to write the last bit of that last abstract lightly.

From: Urocortin, a CRF-like peptide, restores key indicators of damage in the substantia nigra in a neuroinflammatory model of Parkinson's disease...

We are unclear as to the precise mechanism by which UCN I exerts its protective effect. Our unpublished data indicates that UCN I treatment leads to a preservation or restoration of TH+cells in the SNc.

Whether this is the result of cytoprotection, such as might occur due to an anti-inflammatory action, or a stimulation of neurogenesis remains to be determined. One possibility could be that UCN I might reduce the massive astrogliosis which arises in the SNc as a result of LPS toxicity [17]. Additionally, the potential contribution of the SNc relative to the ventral tegmental area in restoring nigrostriatal function is also unclear, although we intend to investigate this.

In summary, our data constitutes the first report of a restoration of key indicators of nigrostriatal damage in a neuroinflammatory model of PD after the lesion has become established by a molecule known to have antiinflammatory properties [7].

Although activation of the HPA axis by a CRF agonist might have potentially deleterious side effects, evidence suggests that these may be averted.

Thus, CRF and UCN both reduced weight gain in rodents but CRF was much more effective than UCN in this respect and only CRF produced effects consistent with increased sympathetic activity[18]. In order to achieve substantial therapeutic relevance a means by which central CRF1 sites can be activated is clearly essential as may be refinement to ensure an appropriate pharmacological response.

While UCN is a relatively large molecule with poor blood brain barrier penetration, recently small, lippophillic, CRF1 selective antagonists have become available and CRF receptor pharmacology is a rapidly expanding field.

As such we consider it highly likely that CRF1 agonists will become available offering new possibilities in the study of UCN mediated neuroprotection as well as being of potential therapeutic value in PD.

http://www.jneuroinflammation.com/content/4/1/19

another article:

http://www3.interscience.wiley.com/c...2818/HTMLSTART

Discussion
Abstract Introduction Materials and methods Results Discussion Acknowledgements References

In the present study we have used a variety of measures, behavioural, neurochemical and histological, that indicate a clear protective role for UCN against 6-OHDA- or LPS-mediated nigrostriatal lesions. These findings support a potential protective role for UCN in these two paradigms of PD and clearly demonstrate that, when UCN is given concomitantly with either 6-OHDA or LPS, a comprehensive reversal of all selected markers of nigrostriatal cellular loss results. Importantly, the effects of UCN were not restricted to when it was coadministered with 6-OHDA or LPS but were also manifest when given 7 days after toxin injection when neurotoxic damage is already becoming well established (present data; He et al., 2000). This suggests that UCN is able to rescue dopaminergic neurones once damage is established. Taken as a whole, our data reveal that UCN can act as a potent neuroprotective agent in two distinct rodent models of PD and at a dose that was found to be effective in a variety of other studies (Brar et al., 2000, 2002; Facci et al., 2003; Choi et al., 2006). Moreover, we have assessed multiple parameters of NS pathway activity and nigral neuronal integrity. This approach has important strengths over 'single-parameter' studies, given that human PD pathology is complex and multicomponent (Tatton et al., 1998; Blum et al., 2001; Gandhi & Wood, 2005). Of particular significance is our finding that UCN is able to arrest and possibly reverse NS lesions once the neurodegenerative process has commenced. This principle (if reproduced in the human brain) would have obvious clinical significance as patients generally present with symptoms only once nigral neuronal loss reaches 70–80% of the total nigral complement and striatal DA levels have fallen significantly (Abercrombie et al., 1990). Apart from an apparent facility for preservation of cells, it is possible that UCN may act to stimulate dopaminergic neurones via several distinct mechanisms. Recent studies have shown that UCN potentiates the release of [3H]DA from electrically stimulated rat striatal slices (Bagosi et al., 2006) and increases the TH mRNA levels expressed by PC12 cells (Nanmoku et al., 2005), a cell type phenotypically related to midbrain dopaminergic neurones. We investigated the possible effects of UCN on TH in intact unlesioned rats by injecting the peptide alone into the SNc. Rats studied 1, 7 and 14 days later showed no significant effect on tissue DA, TH activity or protein levels (data not shown). In the present study, UCN appears to 'reverse' the loss of TH-positive cell bodies, as sections taken from rats killed 7 days post-6-OHDA or post-LPS clearly show fewer TH-positive cells than those treated with UCN at the 7-day time point (Figs 3d and 4dcf.3f and 4f).

The underlying cellular mechanism responsible for this highly significant finding is, as yet, unclear although it is possible that UCN increases expression of TH protein in PC12 cells (Nanmoku et al., 2005). No such effect was observed in the present study in vivo. It is possible that UCN effects a regrowth and remodeling of surviving dendrites as observed by Swinny et al. (2004) using cerebellar Purkinje cells in vitro. Interestingly, Scarabelli et al. (2002) also reported an apparent restorative action of UCN, albeit observed in cardiac myocytes. In addition, it is probable that UCN achieves a neuroprotective effect partly via prevention of apoptotic cell death (Scarabelli et al., 2002; Intekhad-Alam et al., 2004). Our own studies have shown that the peptide significantly reduces the number of end-stage apoptotic nuclei observed in nigral sections following intracerebral 6-OHDA injection (Biggs et al., 2006), a significant finding as apoptosis is an important mechanism in 6-OHDA neurotoxicity (Cutillas et al., 1999) and human PD (Tatton et al., 1998; Mochizuki et al., 1996). Our use of the single-dose LPS PD model (Herrera et al., 2000) increases the significance of our data, given that recent evidence supports a neuroinflammatory component in the aetiology of human PD (Gao et al., 2003b; Block et al., 2007; Whitton, 2007) and that UCN itself possesses anti-inflammatory properties (Gonzalez-Rey et al., 2006). It is possible that UCN is instigating de-novo neurogenesis, presumably from recruited stem cells, as has been postulated in other studies (Borta & Hoglinger, 2007). The determination of this is, however, beyond the scope of the present study. Although it is yet to be proven, we would be inclined to the idea that the peptide is able to rescue DA neurones that would otherwise have been damaged beyond repair as well as possibly stabilizing the nigral environment due to its anti-inflammatory properties. The precise neuroanatomical site at which UCN acts is, as yet, unclear although a local action at the level of nigral cell bodies and dendrites seems likely, given the presence of CRF1 immunoreactivity here (Sauvage & Steckler, 2001) and widespread distribution of UCN in the brain (Yamamoto, 1998; Vasconcelos et al., 2003). Studies utilizing cerebellar granule cells and hippocampal neurones (Pederson et al., 2002) also suggest that the engagement of CRF1 is necessary for neuroprotection. It has recently been shown that UCN II, which has a high selectivity for the CRF2 receptor subtype, is able to block voltage-gated calcium channels in PC12 cells (Tao et al., 2006). These authors have proposed that this could be the basis for neuroprotection. Whether this applies to UCN and could be shown in vivo remains to be seen.

Overall, our results add significantly to a growing knowledge base, whereby UCN mediates cytoprotection in cardiac tissues (Brar et al., 2000, 2002; Scarabelli et al., 2002) and cultured neurones (Pederson et al., 2002; Facci et al., 2003; Choi et al., 2006), with the crucial refinement that we have demonstrated efficacy in two distinct in-vivo models of a currently incurable neuropathology. The apparent ability of UCN to arrest NS damage and possibly stimulate the remaining cells suggests a novel mechanism that, if translated therapeutically, would offer a significant advance in PD treatment. This principle has recently been proposed as an essential prerequisite for the basis of a meaningful advance in PD therapy (Meissner et al., 2004). The rapidly expanding interest in UCN itself and central CRF receptor pharmacology heralds the development of novel small molecule agonists with selectivity for CRF1 and CRF2 subtypes, some of which will probably be suitable for evaluation in pre-clinical and clinical settings. We believe that our studies are an important first step towards validating UCN and central CRF receptors as potential future targets in the treatment of human PD.

cafepharma boards speaks about it?
 

byetta
 

Hi Tena, the drug Rick is discussing is different than Byetta. Byetta is Exenatide. There was a brief discussion concerning byetta:

http://neurotalk.psychcentral.com/sh...ghlight=byetta

(Exenatide is manufactured and marketed by Amylin Pharmaceuticals and Eli Lilly and Company. Exenatide is a synthetic version of exendin-4, a hormone found in the saliva of the Gila monster. It displays biological properties similar to human glucagon-like peptide-1 (GLP-1), a regulator of glucose metabolism and insulin secretion. .. although the mechanism of action is still under study. wikipedia)
Its utility in PD went no where as best I could discern; perhaps the lack of further research of its use in PD was due to a couple of cases of pancreatitis that occurred in patients taking byetta for diabetes.

This is good
 

While I am ready for the usual fine print, this is the most encouraging thing I've seen. An experienced, conservative team says it cured, not protected. A seasoned researcher, and English at that, is putting his professional life on the line when he makes these type of statements. And, best of all, it is already on the shelf! So, how do we guard against another GDNF? Those who have connections with the orgs, forward for funding consideration.

From Urocortin reverses Parkinsonian like effects of intra-nigral lipopolysaccaride injection

2007

The current data provide further evidence for a potential neuroprotective role for UCN inmodels of PD. Given that PD is almost certainly the result of complex multifactorial events, theactions of UCN may be especially fortuitous. By combining both anti-apoptotic and anti-inflammatory properties it may be that UCN combines actions to yield an ‘anti-Parkinsonian’like effect. It is our opinion that the development of CNS permeable ligands for the UCN receptor could constitute a significant development in the therapy of PD.

http://www.pa2online.org/abstracts/V...e2abst156P.pdf

if i understand correctly
 

Urocortin is a peptide produced primarily in the brain. Neurons may have two different types of receptors or "switches" that a urocortin molecule can activate or "turn on". Those two receptors are imaginatively called "1" and "2".

Receptor 1 is part of the stress system and receptor 2 is part of our "appestat" or appetite control.

AmI close so far? If so- Receptor 1 is what we are most interested in. Since it is tied into the stress system, I wonder if this is where our weird stress sensitivity enters the picture in some way?

I wonder, too, if there are ways to boost the supply of "keys" (ligands?) in hopes of triggering a similar effect. Would these be substances that make us feel good? Is this involved with anti-depressant induced neurogenesis?

This helped a bit:

1: Brain Res. 1999 Nov 27;848(1-2):141-52.

A role for corticotropin releasing factor and urocortin in behavioral responses
to stressors.

Koob GF, Heinrichs SC.

Department of Neuropharmacology, CVN-7, The Scripps Research Institute, La Jolla,
CA 92037, USA. gkoob@scripps.edu

Corticotropin-releasing factor (CRF) and CRF-related neuropeptides have an
important role in the central nervous system to mediate behavioral responses to
stressors. CRF receptor antagonists are very effective in reversing
stress-induced suppression and activation in behavior. An additional CRF-like
neuropeptide, urocortin, has been identified in the brain and has a high affinity
for the CRF-2 receptor in addition to the CRF-1 receptor. Urocortin has many of
the effects of CRF but also is significantly more potent than CRF in decreasing
feeding in both meal-deprived and free-feeding rats. In mouse genetic models,
mice over-expressing CRF show anxiogenic-like responses compared to wild-type
mice, and mice lacking the CRF-1 receptor showed an anxiolytic-like behavioral
profile compared to wild-type mice. Results to date have led to the hypothesis
that CRF-1 receptors may mediate CRF-like neuropeptide effects on behavioral
responses to stressors, but CRF-2 receptors may mediate the suppression of
feeding produced by CRF-like neuropeptides. Brain sites for the behavioral
effects of CRF include the locus coeruleus (LC), paraventricular nucleus (PVN) of
the hypothalamus, the bed nucleus of the stria terminalis (BNST), and the central
nucleus of the amygdala. CRF may also be activated during acute withdrawal from
all major drugs of abuse, and recent data suggest that CRF may contribute to the
dependence and vulnerability to relapse associated with chronic administration of
drugs of abuse. These data suggest that CRF systems in the brain have a unique
role in mediating behavioral responses to diverse stressors. These systems may be
particularly important in situations were an organism must mobilize not only the
pituitary adrenal system, but also the central nervous system in response to
environmental challenge. Clearly, dysfunction in such a fundamental
brain-activating system may be the key to a variety of pathophysiological
conditions involving abnormal responses to stressors such as anxiety disorders,
affective disorders, and anorexia nervosa.


PMID: 10612706 [PubMed - indexed for MEDLINE]

1: J Pharmacol Exp Ther. 2004 Nov;311(2):427-40. Epub 2004 Aug 5.

Corticotropin-releasing factor in brain: a role in activation, arousal, and
affect regulation.

Heinrichs SC, Koob GF.

The Scripps Research Institute, Department of Neuropharmacology, CVN-7, 10550
North Torrey Pines Road, La Jolla, CA 92037, USA.

Organisms exposed to challenging stimuli that alter the status quo inside or
outside of the body are required for survival purposes to generate appropriate
coping responses that counteract departures from homeostasis. Identification of
an executive control mechanism within the brain capable of coordinating the
multitude of endocrine, physiological, and functional coping responses has high
utility for understanding the response of the organism to stressor exposure under
normal or pathological conditions. The corticotropin-releasing factor
(CRF)/urocortin family of neuropeptides and receptors constitutes an affective
regulatory system due to the integral role it plays in controlling neural
substrates of arousal, emotionality, and aversive processes. In particular,
available evidence from pharmacological intervention in multiple species and
phenotyping of mutant mice shows that CRF/urocortin systems mediate motor and
psychic activation, stimulus avoidance, and threat recognition responses to
aversive stimulus exposure. It is suggested that affective regulation is exerted
by CRF/urocortin systems within the brain based upon the sensitivity of local
brain sites to CRF/urocortin ligand administration and the appearance of
hypothalamo-pituitary-adrenocortical activation following stressor exposure.
Moreover, these same stress neuropeptides may constitute a mechanism for learning
to avoid noxious stimuli by facilitating the formation of so-called emotional
memories. A conceptual framework is provided for extrapolation of animal model
findings to humans and for viewing CRF/urocortin activation as a continuum
measure linking normal and pathological states.


PMID: 15297468 [PubMed - indexed for MEDLINE]

contraindications?
 

I have not been able to find where urocortin is usually prescribed for diabetes, nor that is has any contraindications...I did find that it used to help control weight as it makes you eat less, which could be a bad side effect if one is already on the lean side, as many here are.

I was curious about this, because I was wondering what would happen if someone who was not diabetic started taking this stuff? Would it make them diabetic, or just help their PD? (Assuming your doc would Rx it for you...). I know a lot of white rats who'd be willing to do this, depending on what else it might to do the body...

Rick et al
 

We're talking about two separate drugs here, correct?

Urocortin and Exenatide.

Exenatide is marketed as Byetta and is available now.

Is Urocortin currently marketed as a drug as well?

Is MJF working on either of these? (Paula) :)

Cal

6 Deaths Reported From Diabetes Drug Byetta
 

6 Deaths Reported From Diabetes Drug Byetta
Cause of Death Varies, but Patients Had Developed Pancreatitis
By Kathleen Doheny


WebMD Health NewsReviewed by Louise Chang, MDAug. 27, 2008 -- Six patients taking the type 2 diabetes drug Byetta are reported to have died after developing pancreatitis. That's according to officials from Amylin Parmaceuticals and Eli Lily & Company, the companies that co-market the drug.

Last week, the FDA reported two deaths and four hospitalizations in Byetta patients who had pancreatitis. The four additional deaths -- announced Tuesday by company officials -- are not connected with the four hospitalizations announced by the FDA. Last week, the FDA also said it plans to strengthen warnings about serious pancreatitis problems linked to the drug.

http://diabetes.webmd.com/news/20080...eaths-reported

ABC news
http://abcnews.go.com/Health/Diabete...ory?id=5604366

Where do you buy this peptide?
 

Hi and thanks for this hopeful posting . Urocortin 1 sounds much better than anything else currently available . A good chance it can reverse g this dreadful disease, no invasive operations, amd no waiting for trials, right? It certainly is what I've been praying for. So why has the interest here waned?

Maybe because its impossible to get any info on its availability? I can't find any evidence of it being available as a drug/injection, given to diabetics . All I can see is that www dot PhoenixPeptide dot com sell this peptide to researchers.


This in itself may be a good lead, if one knew what to do with it. But I don't.

So, does anyone have any further information on the actual drug AVAILABLE to diabetics ?

If it was a drug sold in Europe I would be able to get it prescription-free from my trusted european pharmacist. Hope someone has an answer .Thanks , Pippa

same here, can't find it
 

I could not find it either, except for researchers, and even then, there were indications that the peptide available for research comes from bovine brain (no, thanks). I did read somewhere that we make urocortin on our skin, which is interesting, but not particularly helpful.

Also, should note that there are apparently three urocortins, urocortin, urocortin 2, and urocortin 3. All of my research indicated that only urocortin was helpful; indeed, the articles actually said urocortin 2 and 3 had no effect but plain urocortin had siginificant effect. Yes, very hopeful, but how does one get it, and will the plain urocortin cross the BBB? I did not get a clear answer to that particular question, but will continue to see if I can.

when?
 

Rick, when do you think this will be available or rather allowed for PD patients to start taking?

Going to bring this back to life
 

I was quite excited about this and was trying to understand it here in public when I received a PM from a friend telling me that I had put my big foot down right in the middle of some very sensitive negotiations over patent issues that needed to be resolved to move it toward clinical trials.

I have now been told that those negotiations have gone well and that trials should begin this year! And that it is safe to talk about it again. So, it being Christmas, a little hope for us all makes a good present.

I know more than I did, so I am going to try to clear up some of the confusion. First, we are talking about two different but similar discoveries by the same team led by P.S. Whitton. One is that urocortin acting upon CRF receptors triggered repair. Unfortunately, urocortin does not cross the BBB, plus there are a lot of unknowns about it to be followed up.

The other, and far more exciting, was the discovery that the receptors for a peptide called Glucagon-Like Peptide-1 (GLP-1) triggered similar repair when activated by either GLP-1 itself or an agonist (mimic). The diabetic drug Ex-4, derived from our friend the Gila Monster, is such a mimic and has already passed through many hoops for its diabetic uses that won't have to be repeated. Also, it readily passes the BBB and lasts several hours while GLP-1 lasts only minutes. So, we unexpectedly have a half-approved cure that really cured rats. Not only did it cure rats with PD caused by injecting one particular toxin, it also cured rats with PD caused by a second type of toxin. That is, it cured it in two unrelated models. That's good.

GLP-1 is produced in your gut when you eat and triggers insulin production in the pancreas. But its receptors are found other places including the brain. It also fits into some pretty specific spots in the PD puzzle. For example, two things that have been shown to stop PD are fasting and exercise. If you have ever fasted, after a day or so you aren't hungry. GLP-1 controls appetite. Exercise not only slows PD, it also increases production of GLP-1.

There is quite a bit more, including some white rat opportunities that increase GLP-1, but it looks better than anything that I have seen thus far.

So Merry Christmas! :D

Among the things that increase GLP-1...
 

...and have been "coincidentally" suggested as helpful in PD at one time or another-
1- Exercise
2- Fasting
3- Coconut oil
4- Ginseng
5- Glutamine
6- Whey

Lab Rat T-shirt
 

Thank you Rick for sharing all of this, very promising and offers hope at a great time, since several things that looked so good have "failed" (no need to remind everyone, we all know what they are/were).

I think you and all here that self-experiment should get a t-shirt that says "Lab Rat" on it, Lordy knows it is well-deserved!

Byetta
 

Link from 9/10/2007:
http://neurotalk.psychcentral.com/sh...ghlight=byetta

Link listed in response to this topic on 10/27/08 is incorrect--madelyn






Talent hits a target no one else can hit; Genius hits a target no one else can see. Arthur Schopenhauer

Thanks, Rick. I have glutamine in my lab room, and I'm tempted to take a bit, but I won't!

Thanks for the birthday present; I'm a Christmas eve baby. HUGE snow storm in NYC when I was born. Cars not allowed on the road, but the cop let me go home. Darn, I miss my dad.

After sifting through the options and considering cost, effectiveness, and PD-specific conflicts, it looks like the coconut oil is my choice. Of its eight major components, seven bump up GLP-1 levels. It also provides an explanation for the report in the other thread of the Tampa doctor whose husband benefited from it. I wonder, too, if fish oil has a similar action in addition to anti-inflammatory effects. There seems to be a pattern leading to certain fats.

Much has been made of the fact that Inuits ("Eskimos") have little heart disease. Does anyone know if they have much PD?

Fish oil does seem to double GLP-1 levels, at least under the conditions described below. Somewhere in the last year I read a news story about the lone survivor of a mining accident in West Virginia who was virtually brain dead. In desperation, his GP pumped him full of fish oil for several weeks and he was making a strong recovery. Interesting.


1: Regul Pept. 1999 Apr 30;80(3):101-6.

Inhibition of human gastric lipase by intraduodenal fat involves glucagon-like
peptide-1 and cholecystokinin.

Wøjdemann M, Riber C, Bisgaard T, Sternby B, Larsen S, Rehfeld JF, Holst JJ,
Olsen O.

Department of Surgery, Rigshospitalet, National University Hospital, Copenhagen,
Denmark. rh01977@rh.dk

Seven healthy volunteers were intubated with two double lumen nasogastric tubes,
one in the stomach, the other in the duodenum. This system allows simultaneous
sampling of gastric juice and separate intraduodenal perfusion with a dietary fat
(fish oil, 1269 kJ). Gastrin-17 was infused i.v. at a rate of 40 pmol/kg/h
throughout the study. Gastric lipase was measured at 15-min intervals as activity
(tributyrin) and as immunoreactivity (ELISA). Infusion of gastrin-17 resulted in
a stable increase in the plasma concentration from a basal concentration of 8.3
+/- 0.8 pmol/l to 41.4 +/- 4.2 pmol/l. Perfusion with fat reduced gastric lipase
activity from 24.2 +/- 5.3 to 7.2 +/- 2.5 kU/l (P < 0.05), and immunoreactivity
from 0.7 +/- 0.1 to 0.42 +/- 0.1 mg/l (P < 0.05). After termination of fat
perfusion, gastric lipase secretion increased again, though not reaching
preinhibitory concentrations. During the intraduodenal perfusion with fat the
plasma concentrations of glucagon-like peptide-1 (GLP-1) and cholecystokinin
(CCK) increased from 6.9 +/- 0.5 to 15.1 +/- 1.5 pmol/l (P < 0.05) and from 1.2
+/- 0.4 to 3.8 +/- 0.9 pmol/l (P < 0.05). This study reveals a negative effect of
fat in the duodenum on gastric lipase secretion. This effect may be mediated by
GLP-1 and/or CCK.


PMID: 10425652 [PubMed - indexed for MEDLINE]

http://www.setma.com/article.cfm?ID=292


"The recent return home of the only survivor of the Sago mine disaster, Randall McCloy Jr., seems miraculous and it was. Yet, there is a sound basis for his recovery. McCloy, who had suffered heart, kidney, and liver failure in addition to brain failure, returned home less than four months after the mining disaster. One of the principle reasons for this recover was Dr. Bailes’ administering of very high doses of Omega 3 Fish Oil to McCloy.

McCloy received (and continues to take) 15 grams per day of EPA and DHA. Although a seemingly extraordinarily high dose, McCloy’s blood levels of these fatty acids were constantly monitored to maintain them within a therapeutic zone to maximize the reduction of systemic inflammation without compromising the body’s ability to fight infection.

The implications of Randall McCloy’s remarkable recovery have widespread medical importance, not only for brain trauma patients, but also for any patient with neurological disorders. It has been demonstrated by Harvard Medical School that high-dose fish oil has significant benefits in treating bipolar depression, and a recent study demonstrated the same levels used by Dr. Bailes in treating Randall McCloy also demonstrated significant improvement in children with ADHD. Maybe this is why our grandmother called fish oil "brain food."

Glp-1
 

any further information about this topic? madelyn

The last I heard....
 

...Tom Isaacs' Parkinson's Trust was funding a hush-hush clinical trial. I have been trying to catch Tom in his office long enough to get an update with little success. I'll report once I know more.

Here is a tantalizing tidbit...
 

The work in progress uses a diabetes drug called Ex-4. Ex-4 is a mimic of a hormone called GLP-1. GLP-1 is produced in the gut but has receptors in the brain as well. The excitement is that stimulating the brain receptors cured the PD rats (RWP, I guess :D ). Not "slowed progression" nor "relieved symptoms." For the first time it has been claimed "cured."

Normally, GLP-1 is made in the gut and a little makes it into the blood but is supposedly quickly broken down by enzymes and only a little makes it to the brain. The idea is to use enzyme-resistant versions of GLP-1 (Ex-4 being one) to increase what gets to the brain.

But it seems to me that if there are other ways to increase the amount of GLP-1 in the blood that that is worth considering. And there are things that do increase it and some of them are already thought helpful in PD.

Exercise increases GLP-1 levels, for example. Certain oils do, too. And now it seems that the "Rosebud Low Glycemic Diet" does too.

"It's been discovered that eating a meal with a low GI (glycemic index) increases gut hormone production, which leads in turn to suppression of appetite and the feeling of fullness. This new research was presented at the annual Society for Endocrinology meeting in the U.K."
from http://shamvswham.blogspot.com/2009_03_01_archive.html

We already know that PWP have glycemic issues, that Ldopa makes them worse, and that some researchers suspect Alzheimer's to be a glycemic problem too. And we know that GLP-1 is a potent player in the production of insulin. Coincidence?

don't think so
 

...and I read somewhere that many consider Alzheimer's to be a third type of diabetes, so this would make a lot of sense, particularly when you consider that the brain uses a vast portion of the oxygen and glucose we take in. Thanks.

Received this update today
 

We, The Cure Parkinson’s Trust, continue to be extremely excited about the prospects for treating Parkinson’s with Exendin, and we are currently trying to secure funding to conduct a major UK clinical trial to evaluate its use in a large group of patients. We are now in talks with prospective Principal Investigators of this clinical trial in order to develop the most appropriate study protocol, which will include measurement of both motor and non-motor benefits (since laboratory research suggests Exendin, uniquely, promises to help in both areas)









Tom Isaacs

Co-Founder - The Cure Parkinson's Trust

Board Member - EPDA

01923 777015

www.cureparkinsons.org.uk

Now I will add my two cents
 

Tom-
I will forward this to you in case you don't catch it here. Given that Exendin has already been evaluated and approved for other uses, some of us are going to attempt to persuade our own doctors to work with us to perform our own trials. It would possibly be to everyone's benefit if there was some standardization of effort. I am thinking of a single page outlining the proposed trial plus a section of "Before and after" data for our own doctors to fill in and forward to a central location for compiling.

I know this is a radical idea, but so what? :D
-Rick

Exendin-4
 

Rick,
Didn't Olsen post about Exendin in 2007?
Ron

http://neurotalk.psychcentral.com/sh...ad.php?t=27716

Swedes Show Byetta Cures Parkinson's Disease in Rats (2 Ratings) 7-Sep-07 06:10 pm Peptide hormone exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain and induces recovery in an animal model of parkinson's disease.

Bertilsson G, Patrone C, Zachrisson O, Andersson A, Dannaeus K, Heidrich J, Kortesmaa J, Mercer A, Nielsen E, R?olm H, Wikstr?.

NeuroNova AB, Stockholm, Sweden.

We investigated the effects of exendin-4 on neural stem/progenitor cells in the subventricular zone of the adult rodent brain and its functional effects in an animal model of Parkinson's disease. Our results showed expression of GLP-1 receptor mRNA or protein in the subventricular zone and cultured neural stem/progenitor cells isolated from this region.

In vitro, exendin-4 increased the number of neural stem/progenitor cells, and the number of cells expressing the neuronal markers microtubule-associated protein 2, beta-III-tubulin, and neuron-specific enolase.

When exendin-4 was given intraperitoneally to naive rodents together with bromodeoxyuridine, a marker for DNA synthesis, both the number of bromodeoxyuridine-positive cells and the number of neuronal precursor cells expressing doublecortin were increased.

Exendin-4 was tested in the 6-hydroxydopamine model of Parkinson's disease to investigate its possible functional effects in an animal model with neuronal loss. After unilateral lesion and a 5-week stabilization period, the rats were treated for 3 weeks with exendin-4. We found a reduction of amphetamine-induced rotations in animals receiving exendin-4 that persisted for several weeks after drug administration had been terminated.

Histological analysis showed that exendin-4 significantly increased the number of both tyrosine hydroxylase- and vesicular monoamine transporter 2-positive neurons in the substantia nigra.

In conclusion, our results show that exendin-4 is able to promote adult neurogenesis in vitro and in vivo, normalize dopamine imbalance, and increase the number of cells positive for markers of dopaminergic neurons in the substantia nigra in a model of Parkinson's disease.

Yes, Ron, that's the one
 

Here's what I have on it. Not exactly the new kid on the block but it does seem to be a race between two or three research teams-


1: Li Y, Perry T, Kindy MS, Harvey BK, Tweedie D, Holloway HW, Powers K, Shen H,
Egan JM, Sambamurti K, Brossi A, Lahiri DK, Mattson MP, Hoffer BJ, Wang Y, Greig
NH. GLP-1 receptor stimulation preserves primary cortical and dopaminergic
neurons in cellular and rodent models of stroke and Parkinsonism. Proc Natl Acad
Sci U S A. 2009 Jan 27;106(4):1285-90. Epub 2009 Jan 21. PubMed PMID: 19164583;
PubMed Central PMCID: PMC2633544.

2: Harkavyi A, Abuirmeileh A, Lever R, Kingsbury AE, Biggs CS, Whitton PS.
Glucagon-like peptide 1 receptor stimulation reverses key deficits in distinct
rodent models of Parkinson's disease. J Neuroinflammation. 2008 May 21;5:19.
PubMed PMID: 18492290; PubMed Central PMCID: PMC2426681.

3: Bertilsson G, Patrone C, Zachrisson O, Andersson A, Dannaeus K, Heidrich J,
Kortesmaa J, Mercer A, Nielsen E, Rönnholm H, Wikström L. Peptide hormone
exendin-4 stimulates subventricular zone neurogenesis in the adult rodent brain
and induces recovery in an animal model of Parkinson's disease. J Neurosci Res.
2008 Feb 1;86(2):326-38. PubMed PMID: 17803225.

4: Abuirmeileh A, Harkavyi A, Lever R, Biggs CS, Whitton PS. Urocortin, a
CRF-like peptide, restores key indicators of damage in the substantia nigra in a
neuroinflammatory model of Parkinson's disease. J Neuroinflammation. 2007 Jul
21;4:19. PubMed PMID: 17659087; PubMed Central PMCID: PMC1976313.

5: Perry T, Holloway HW, Weerasuriya A, Mouton PR, Duffy K, Mattison JA, Greig
NH. Evidence of GLP-1-mediated neuroprotection in an animal model of
pyridoxine-induced peripheral sensory neuropathy. Exp Neurol. 2007
Feb;203(2):293-301. Epub 2006 Nov 22. PubMed PMID: 17125767; PubMed Central
PMCID: PMC1850958.

6: Perry T, Greig NH. Enhancing central nervous system endogenous GLP-1 receptor
pathways for intervention in Alzheimer's disease. Curr Alzheimer Res. 2005
Jul;2(3):377-85. Review. PubMed PMID: 15974903.

7: Greig NH, Mattson MP, Perry T, Chan SL, Giordano T, Sambamurti K, Rogers JT,
Ovadia H, Lahiri DK. New therapeutic strategies and drug candidates for
neurodegenerative diseases: p53 and TNF-alpha inhibitors, and GLP-1 receptor
agonists. Ann N Y Acad Sci. 2004 Dec;1035:290-315. Review. PubMed PMID: 15681814.

8: Perry TA, Greig NH. A new Alzheimer's disease interventive strategy: GLP-1.
Curr Drug Targets. 2004 Aug;5(6):565-71. Review. PubMed PMID: 15270203.

9: During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, Bland RJ,
Klugmann M, Banks WA, Drucker DJ, Haile CN. Glucagon-like peptide-1 receptor is
involved in learning and neuroprotection. Nat Med. 2003 Sep;9(9):1173-9. Epub
2003 Aug 17. PubMed PMID: 12925848.

10: Perry T, Lahiri DK, Sambamurti K, Chen D, Mattson MP, Egan JM, Greig NH.
Glucagon-like peptide-1 decreases endogenous amyloid-beta peptide (Abeta) levels
and protects hippocampal neurons from death induced by Abeta and iron. J Neurosci
Res. 2003 Jun 1;72(5):603-12. PubMed PMID: 12749025.

11: Drucker DJ. Glucagon-like peptides: regulators of cell proliferation,
differentiation, and apoptosis. Mol Endocrinol. 2003 Feb;17(2):161-71. Review.
PubMed PMID: 12554744.

12: Perry T, Greig NH. The glucagon-like peptides: a new genre in therapeutic
targets for intervention in Alzheimer's disease. J Alzheimers Dis. 2002
Dec;4(6):487-96. Review. PubMed PMID: 12515900.

13: Perry T, Haughey NJ, Mattson MP, Egan JM, Greig NH. Protection and reversal
of excitotoxic neuronal damage by glucagon-like peptide-1 and exendin-4. J
Pharmacol Exp Ther. 2002 Sep;302(3):881-8. PubMed PMID: 12183643.

14: Perry T, Lahiri DK, Chen D, Zhou J, Shaw KT, Egan JM, Greig NH. A novel
neurotrophic property of glucagon-like peptide 1: a promoter of nerve growth
factor-mediated differentiation in PC12 cells. J Pharmacol Exp Ther. 2002
Mar;300(3):958-66. PubMed PMID: 11861804.

15: Oka JI, Goto N, Kameyama T. Glucagon-like peptide-1 modulates neuronal
activity in the rat's hippocampus. Neuroreport. 1999 Jun 3;10(8):1643-6. PubMed
PMID: 10501550.

16: Göke R, Larsen PJ, Mikkelsen JD, Sheikh SP. Distribution of GLP-1 binding
sites in the rat brain: evidence that exendin-4 is a ligand of brain GLP-1
binding sites. Eur J Neurosci. 1995 Nov 1;7(11):2294-300. PubMed PMID: 8563978.

Extendin home-style trial protocols....
 

Rick,

I am seeing a new neuro Tuesday and have no idea what to expect. Do you have a written protocol for your proposed independent trials? If so, I'd like to take a copy along with me.

At the very least it could help weed out uncooperative mds! Thanks, Ibby

First impressions are so important..
 

:D
No, I have no written protocol. I don't know if it has gotten that far or not. Why not get a copy of the Whitton paper (look back near the start of this thread) and go to Medline and download the PDF (It is available for free). Take it with you and introduce the subject by telling the neuro that you realize that he doesn't know anything about a diabetes medicine and could he suggest an endocrinologist that he would be comfortable working with to pursue this. If he starts foaming at the mouth, remind him that the drug has passed the FDA hoops already and that there is respectable, peer reviewed research to justify an off label trial. If he goes for it, I want his name. :D

If not, you might try your GP. Mine has volunteered to help if I can get him enough data to cover himself. I intend to discuss with him just how much that might be later this year. Good luck.