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 ). 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?

...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.

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

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?
-Rick

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.

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.

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

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.

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.