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.