I suspect there could be some support for Prana to progress PBT434. Dr Shoulson is also founder of the Parkinsons Study Group, so you can be sure they are aware of a technology with such spectacular preclinical results.
"Now, Bush and colleagues have discovered that samples of human brain tissue affected by Parkinson's disease contain lower levels of soluble tau but elevated levels of iron. This lack of tau protein, they suggest, could increase iron levels in the brain and cause neurodegeneration. "
"Treating a tau KO mouse with an iron chelator was not an experiment you would have predicted to be obvious from the existing literature,' says Bush. 'We were quite stunned by how profoundly clioquinol rescued the tau KO mice.' A further experiment revealed that a lack of tau impairs the trafficking of a protein involved in neuronal iron export.
Patrick Lewis, who investigates neurodegenerative diseases at University College London, UK, says: 'This paper suggests that complete loss of tau can also lead to neurodegeneration, and it is of great interest that iron is involved in this process as there are a number of rare forms of Parkinsonism that are linked to brain iron accumulation . Therapeutic approaches that are being developed that target all forms of tau, such as immunotherapies or production inhibitors, could cause more damage than good.'
Interesting that the brain cancer drug PBT519, is at the same stage as the Parkinsons drug. Clioquinol, the predecessor of PBT2 has been tested against myeloma in Canada. Low intracellular levels of the drug were cited as the reason they saw no effect. PBT2 with 20 times the ability to pass the blood brain barrier and may be the answer to that problem. Preclinicals of 519 looked good.
Clin Lymphoma Myeloma Leuk. 2012 Oct;12(5):330-6. doi: 10.1016/j.clml.2012.05.005. Epub 2012 Jun 9.
Clioquinol is a small-molecule metal ionophore that inhibits the proteasome through a metal-dependent mechanism. Here, we report a phase I study of clioquinol in patients with refractory hematologic malignancies. Neuropathy and abdominal pain were dose-limiting toxicities. Minimal pharmacodynamic effects were observed, and there were no clinical responses.
Clioquinol is a small-molecule metal ionophore that inhibits the enzymatic activity of the proteasome and displays preclinical efficacy in hematologic malignancies in vitro and in vivo. Therefore, we conducted a phase I clinical trial of clioquinol in patients with refractory hematologic malignancies to assess its safety and determine its biological activity in this patient population.
Sixteen cycles of clioquinol were administered to 11 patients with 5 patients reenrolled at the next dose level as per the permitted intrapatient dose escalation. Dose-limiting neurotoxicity and abdominal pain were observed at a dose of 1600 mg twice daily. Intracellular drug levels were low. Minimal inhibition of the proteasome was observed. No clinical responses were observed.
CONCLUSION:In patients with refractory hematologic malignancies, the maximal tolerated dose of clioquinol was determined. Minimal inhibition of the proteasome was observed at tolerable doses, likely due to low intracellular levels of the drug.
Sentiment: Strong Buy
I believe you're right that the Phase I has been shifted to 2015. I had the impression that Prana planned to self-fund the Phase I, and that the stuff funded by both the MJFF and Parkinson's UK was purely pre-clinical.
I think that Prana was sort of counting on the results of the IMAGINE trial to boost the share price to the point where the company could easily raise cash for multiple parallel trials (HD, AD, PD). Since that bubble burst, Prana is having to scale back its near-term plans.
Very sleuthy of you to make that conclusion . I haven't looked at my scottrade acct since the end of march . Wayyyy to depressing to look at right now . Still getting anxiety thinking about it . First GALE recovery . Now this . If only the PRAN people would say something ...I would find that very helpful .
If you get in under $2 on this piece of ****, you will make more then 100% upside by holding a few months. The sell off places shares well below actual cash value.
Sentiment: Strong Buy
Does it anywhere indicate the Parkinson's UK (not MJFF) grant at the University of Leeds is a human study? I have assumed it's pre-clinical. Prana stated only once that first in human studies were targeted in 2014 year, and has reverted back to 2015 target for first in human studies of PBT434. I have seen nothing about the University of Leeds study going beyond pre-clinical/non-human work. I hope I am wrong. I reviewed the Parkinson's UK website and they seem to be an independent charity from MJFF.
went up 8% after I posted, nothing to do with my post, but you got to play your cards right..
Sentiment: Strong Buy
Go to the Prana Biotechnology website, and they have a graphic (under the "Products" buttton in the upper right hand corner) of the different drugs that are in process (including PBT2, PBT434, PBT519) and at what stage (screening onwards). PBT519, for brain cancer, for example, is listed at the same phase in the process as PBT434 (for Parkinson's).
ALZFORUM WEBINAR Noon, Tuesday, April 22, 2014
In Alzheimer's disease, preclinical hopes too often have been dashed by clinical failure. While amyloid plaques can be cleared and memory restored in mice, the same is not yet true for people. Are mice too different, or do the models lack a certain je ne sais quoi? Researchers led by Takaomi Saido at RIKEN, Japan, have created a different type of model. These APP knock-ins make human Aβ from the mouse APP locus and develop amyloid pathology without overexpressing APP or any of its other cleavage fragments. Those pile up in mice expressing human transgenes, muddling interpretation of the various phenotypes.
Compare Saido's and older APP strains on Alzforum's new Research Models
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will join him for a panel for a discussion.
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"Be patient and you will be rewarded." Well, I've been patient with Prana for nearly eight years now. My only reward came from selling off about 37% of my shares during the run-up before the recent clinical trial results. This turned out to be a big reward indeed. Multiple hundreds of percent gain, nearly all of which was realized shortly before the results were announced. The shares that I still own are up about 25% from where I bought them. So if I had possessed the absolute faith in Prana that some people here exhibit and had kept all my shares and held them through the results, my reward would have been minuscule.
This will be a Phase I trial of PBT434 on healthy volunteers to assess safety. I don't anticipate a Phase II trial of PBT434 anytime soon, due to Prana's chronic lack of money. I suspect that they'll focus on PBT2 for Huntington's for the time being.