Another Potential Treatment for PD
 

Where are the drug companies when it comes to developing drugs used for other diseases or other well known older drugs like dextromethorphan and naltrexone? While we have to hope for a cure, why can't they develop an existing drug that has been shown to slow or stop PD progression in research laboratories like the NIH? From what I've read, preventing microglia from being over activated will stop or slow PD. GLP-1 appears to do this.


If anyone is corresponding with the MJFF, maybe they would find the below papers useful.
Ashley

http://www.pnas.org/content/106/4/1285.full

Glucagon-like peptide-1 (GLP-1) is an endogenous insulinotropic peptide secreted from the gastrointestinal tract in response to food intake. It enhances pancreatic islet β-cell proliferation and glucose-dependent insulin secretion, and lowers blood glucose and food intake in patients with type 2 diabetes mellitus (T2DM). A long-acting GLP-1 receptor (GLP-1R) agonist, exendin-4 (Ex-4), is the first of this new class of antihyperglycemia drugs approved to treat T2DM. GLP-1Rs are coupled to the cAMP second messenger pathway and, along with pancreatic cells, are expressed within the nervous system of rodents and humans, where receptor activation elicits neurotrophic actions. We detected GLP-1R mRNA expression in both cultured embryonic primary cerebral cortical and ventral mesencephalic (dopaminergic) neurons. These cells are vulnerable to hypoxia- and 6-hydroxydopamine–induced cell death, respectively. We found that GLP-1 and Ex-4 conferred protection in these cells, but not in cells from Glp1r knockout (-/-) mice. Administration of Ex-4 reduced brain damage and improved functional outcome in a transient middle cerebral artery occlusion stroke model. Ex-4 treatment also protected dopaminergic neurons against degeneration, preserved dopamine levels, and improved motor function in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease (PD). Our findings demonstrate that Ex-4 can protect neurons against metabolic and oxidative insults, and they provide preclinical support for the therapeutic potential for Ex-4 in the treatment of stroke and PD.

http://joe.endocrinology-journals.or...ract/202/3/431
Exendin-4 is a naturally occurring more potent and stable analog of glucagon-like peptide-1 (GLP-1) that selectively binds at the GLP-1 receptor. It has been recently demonstrated that GLP-1 receptor stimulation preserves dopaminergic neurons in cellular and rodent models of Parkinson's disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic neurotoxicity in rodents; previous studies suggest that activated microglia actively participate in the pathogenesis of PD neurodegeneration. However, the role of microglia in the neuroprotective properties of exendin-4 is still unknown. Here, we show that, in the mouse MPTP PD model, systemic administration of exendin-4 significantly attenuates the loss of substantia nigra pars compacta (SNpc) neurons and the striatal dopaminergic fibers. Exendin-4 prevents MPTP-induced microglial activation in the SNpc and striatum, and the expression of matrix metalloproteinase-3. In addition, exendin-4 also suppressed MPTP-induced expression of pro-inflammatory molecules and tumor necrosis factor http://joe.endocrinology-journals.org/math/alpha.gif and interleukin-1β. Our data indicate that exendin-4 may act as a survival factor for dopaminergic neurons by functioning as a microglia-deactivating factor and suggest that exendin-4 may be a valuable therapeutic agent for neurodegenerative diseases such as PD.

One word: Greed
 

Ashley,

Thanks for broaching this topic. I've often wondered if some of us don't ask our neuros for off-label prescriptions based on initial research findings. For example, Isradipine, a calcium channel blocker normally prescribed for high blood pressure, is in clinical trials right now as it has halted progression in animal models. The problem is always, how much do we need to take for the drug to be therapeutic. Not to mention the possible relationship between subtypes and efficacy of drugs- we won't all necessarily benefit from the same off-label drugs, so if it's not beneficial, is it safe?

The reason pharmas do not pursue applying older, more established drugs to treatment of Parkinson's? There is no patent to be filed, no blockbuster drug to market, and not enough profit to be made- same reason herbals and nutritional supplements are largely ignored. From what I know; I'm certainly not an expert, just a lapsed idealist. Not to mention that it takes forever, if it ever does happen, for the FDA to approve off-label use of an existing drug Istradefylline- in face we have a thread on that one. Instead, PWP in Japan will benefit from that one pretty quickly...it's on target for approval there.

Laura

EX4 or byetta
 

My understanding is that EX4 is Byetta, prescribed for diabetes. Our neuro was not interested in prescribing this for us (no surprise there, really) but an alternative out of state doc we consult with was....provided we work with an endocrinologist in our town. His concern was that since we do not have diabetes, but would be taking a drug used to treat it, we could have some real problems (like passing out!). He wanted close monitoring which of course he cannot do being out of state. It's really scary to think about actually taking a drug for something like diabetes when you don't have that condition---what all might happen?

We are considering proceeding anyway, and are trying to find a good endocrinologist to guide us along the way. He/she may well scare us enough to not take this white rat challenge, but we'll see.

PS We also tried to get our neuro to help us figure out how much methylene blue to use and that was a no-go too. No doubt he laughs his a#@! off when we leave his office, but he's not offering up much himself other than the same-old same-old, so we have nothing to lose by asking.

byetta
 

Friend recently was given a prescription by her physician for Byetta for weight loss. My friend does not have diabetes, and other than a weight problem is healthy. Byetta is only in an injectable form. the only close monitoring my friend has is a monthly fasting blood glucose. Thus, there is "off label" use of Byetta.
There have been rare occurrances of pancreatitis associated with byetta; still my husband would be very interested in a clinical trial of byetta.

Glp-1
 

The last I heard, Tom Isaac's group was funding a trial of some sort but everyone was moving cautiously due to patent issues.

My own GP has said that if I can get him enough documentation that he would prescribe byetta and I may take him up on it.

As for methyline blue, I've got quite a bit of documentation on it but I need to pull it together. Will try to do that over the next few days.

Byetta is also being trialed with Glucagon, in a once a week dosing format for weight loss. This combo is in animal testing right now.

I do know that Byetta is not doing well financially, for its maker, and there is a big push on the sales force now for it and many many samples.

So you will see it in the press more now than earlier.

Before going on this drug, here are some FDA reports collected from MedWatch:
http://patientsville.com/medication/...de_effects.htm

scroll down for them.