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CRIS Moving... this time on good volume so far today. need volume. this is marked up as an "upsidedown head and shoulders" continuation pattern. often this retests the neckline. If volume comes back, and it will.... major clinical news soon... anticipation huge.... macd and volume will kick through the red lines on here.
6.3 million shares moved yesterday... from average volume of like 6,000... will be interesting to see what the new average daily volume falls back to.
from Huntington's Disease Society website:
http://www.hdsa.org/research/news/copperchelation.html
Oxidation, Oligomerization, Copper, and Protein Clearance
Prana Biotech is gearing up for a Phase II clinical trial of its copper chelator in the United States and Australia. As members of the HD community consider participation, it seems like a good time to review the research behind this effort.
Studies by Jonathan Fox, Steven Hersch, and colleagues provide data which suggests that the Huntington's disease protein and its fragments are subject to oxidation by an increased level of copper and that this causes the formation of oligomers, very small aggregates. They also provide data that suggests that preventing oligomer formation enhances the clearance of the soluble protein. Enhancing the clearance of the HD protein could mitigate its toxic effects and therefore preventing oxidation by lowering the levels of copper could be neuroprotective.
In a 2007 study, they first showed that copper interacts directly with the N171 protein fragments that are characteristically produced in the HD brain. Copper promoted oligomerization while the introduction of a copper chelator (either the antibiotic clioquinol or EDTA, a component of green tea) inhibited oligomerization.
They also found that the R6/2 mouse showed an early elevation of copper. However, this mouse model gets sick very quickly and more closely models Juvenile Huntington's disease or late stage HD. The knock in mouse more closely models the course of adult Huntington's disease and in this mouse, copper elevation appeared to occur later. If this is the case, then a clinical trial of a copper chelator (something which binds with a metal ion and removes it from solution), is promising although it might be given a lower priority than a drug which targets an earlier, upstream pathology.
However, the 2011 study suggests that perhaps an early, not easily detectable, elevation of copper might be implicated. Working with the N171 fragment, they found that even a very small amount of copper promotes oligomerization and reduces protein clearance by oxidizing the four cysteine residues on the protein fragment. When those residues were genetically altered, oligomerization was completely blocked even in the presence of copper. They also found that the N590 fragment (the one produced by caspase 6) formed oligomers faster in the presence of copper and protein clearance was reduced.
We have evidence that chelating copper is helpful to a model of Huntington’s disease. In 2005, Dr Steven Massa and colleagues from the San Francisco VA Medical Center reported that clinoquil, an earlier version of the Prana drug, was helpful to the R6/2 mouse mice. The experimental animals lived 20 percent longer than the control animals, performed better on the rotarod test, had less weight loss and less striatal atrophy, and normalized their blood glucose and insulin levels. They accumulated one fourth of the HD protein as the control group.
Clioquinol is a topical antibiotic that was banned from internal use in in 1970 after it was discovered to cause neurotoxicity, a syndrome called subacute myelo-optico-neuropathy (SMON). The reason for this is not understood. Prana was unable to remove toxic impurities in clioquinol and has developed a second generation version of the drug called PBT2 which is the one being used in Alzheimer’s and Huntington’s disease trials.
In a Phase IIa trial. PBT2 significant decreased the beta-amyloid protein in the cerebrospinal fluid and significantly improved executive function in mild Alzheimer’s Disease patients after three months of treatment. A Phase IIb trial is now in progress.
The supporting AD model data has also been published and work is continuing on mechanism. In 2008, Dr. Allard and colleagues reported that PBT2 reduced the soluble AD beta amyloid protein and improved cognition, outperforming clinoquinol. Early this year, Dr. Allard and colleagues reported that PBT2 rescued deficits in hippocampal dendritic spine density and elevated levels of proteins involved in synaptic function and learning and memory, including BDNF (brain derived neurotropic factor), a protein known to be reduced in the brains of HD patients.
Huntington’s disease animal model data for PBT2 has not yet been published in a journal but was presented at the recent 2011 World Congress in Australia. Movement improved in a mouse model of HD and survival time was increased 40 percent, a significant increase compared to the 2005 study of clioquinol.
Prana is recruiting approximately 100 people with early stage Huntington’s disease at 14-16 sites in the United States and Australia. Patients will be followed for six months and the drug will be assessed for safety, tolerability, and efficacy. Two sites in the U.S. have already been named, Massachusetts General and Johns Hopkins. Prana hopes to be able to have results by the end of 2013.
References:
Paul A. Adlard, Laura Bica, Anthony R. White, Milawaty Nurjono, Gulay Filiz, Peter J. Crouch, Paul S. Donnelly, Roberto Cappai, David I. Finkelstein, Ashley I. Bush. “Metal Ionophore Treatment Restores Dendritic Spine Density and Synaptic Protein Levels in a Mouse Model of Alzheimer's Disease.” PLoS One. 2011; 6(3): e17669.
Paul A. Adlard, Robert A. Cherny, David I. Finkelstein, Elisabeth Gautier, Elysia Robb, Mikhalina Cortes, Irene “Rapid Restoration of Cognition in Alzheimer's Transgenic Mice with 8-Hydroxy Quinoline Analogs Is Associated with Decreased Interstitial Aß.” Neuron 2008 Jul 10;59(1):43-55.
Jonathan Fox, Teal Connor, Megan Stiles, Jibrin Kama, Zhen Lu, Kathryn Dorsey, Gregory Liebermann, Ellen Sapp, Robert Cherny, Mary Banks, Irene Volitakis, Marian DiFiglia, Oksana Berezovska, Ashley Bush, Steven Hersch. “Cystein Oxidation within N-Terminal Mutant Huntingtin Promotes Oligomerization and Delays Clearance of Soluble Protein.” The Journal of Biological Chemistry 2011 Mar 30. [Epub ahead of print]
Jonathan H. Fox, Jibrin A. Kama, Gregory Lieberman, Raman Chopra, Kate Dorsey, Vanita Chopra, Irene Volitakis, Robert A. Cherny, Ashley I. Bush, Steven Hersch, ”Mechanisms of Copper Ion Mediated Huntington's Disease Progression.” PLoS ONE 2(3): e334. doi:10.1371/journal.pone.0000334
Lars Lannfelt, Kaj Blennow, Henrik Zetterberg, Stellan Batsman, David Ames, John Harrison, Colin L. Masters, Steve Targum, Ashley I Bush, Ross Murdock, Janet Wilson, and Craig W. Ritchie . “Safety, efficacy, and biomarker findings of PBT2 in targeting Aß as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial.” The Lancet Neurology Volume 7, Issue 9, Pp. 779-86 September 2008.
Trent Nguyen , Aaron Hamby, and Steven M. Massa. “Clioquinol down-regulates mutant huntingtin expression in vitro and mitigates pathology in a Huntington's disease mouse model.” Proceedings of the Nat'l Academy of Sciences of the USA. August 16, 2005 , vol. 102, 11840-5.
Prana Biotech press releases
- Marsha L. Miller, Ph.D., October 5, 2011
I see there is appropriate follow through on TASE:
+19%
Volume 14,582,007
Autophagy proteins are host proteins. They are required for the first rounds of translation of HCV RNA
Since they are host proteins, they "can't" mutate.
http://m.pnas.org/content/early/2009/07/31/0907344106
cool.
I saw that too.
One of theses shares is 10 of the TASE shares and 8.6 Million traded over there.
123,000,000 ordinary shares (12.3 million)
3.7 million on nasdaq so far today.
Big volume over here.
What is the average daily volume on TASE?
yes, my guess is they think that some near term catalyst will give them more leverage next time.
$3 strong support.
no one loves it.
Barton Biggs says he is 65% net long and that if a rally takes off he would feel left behind, and of course he said he's not short enough, should things go south... so I guess it's one day at a time.
they raised on november 2
CORAL GABLES, Fla., Nov. 2, 2011 (GLOBE NEWSWIRE) -- Catalyst Pharmaceutical Partners, Inc. (Nasdaq:CPRX - News) announced today that it has closed its previously announced offering of: (i) 3,046,740 shares of its common stock, and (ii) common stock purchase warrants to purchase an aggregate of 1,523,370 shares of the Company's common stock, to institutional investors in a firm commitment underwritten public offering. The offering price for each share and corresponding warrant was $1.15, and the gross proceeds raised in the offering was $3,503,751. After underwriting discounts and commissions and expenses of the offering payable by the Company, Catalyst expects to receive net proceeds of approximately $3,150,000. Catalyst plans to use the net proceeds from this offering to fund costs associated with the Company's currently ongoing clinical trials and studies and for general corporate purposes.
http://finance.yahoo.com/news/Catalyst-Pharmaceutical-pz-3593160961.html?x=0&.v=1
with the intent to not spam the board with too much off topic stuff, here is a link to a few charts, including ARIA:
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=71104855
could be... whole market was so euphoric this week, instead of pulling back before oex.
google weakness is going to be talked about all next week and will be the reason for comp to sell off.
[OT] What do you make of the gaps on the compq? the two gaps near the 200sma are ripe for picking and testing that old neckline, but I feel so strange that the market didn't "pull back" the week before OEX.
the first chart below is from yesterday, the rest are from other days. I have been putting a crooked slant on "head and shoulders" and seeing how things recover.
[OT] broad market...
Funny how at New Years every head on TV was bemoaning 2011 being an almost perfectly flat year, and today people are realizing how strong this January has been.
Turns out, that price point on the nasdaq is also exactly the old neckline of last year's head and shoulders top.
now the market has consolidated nicely, and broken out, but I don't think there will be new 52 week highs until things pull back.
Nasdaq still has two gaps to fill near, one just under the 50sma.
Sweet. I hope either the gap closes in a month, or that there is a 10M share day that pushes PPS away from the 50sma.
http://stockcharts.com/h-sc/ui?s=EGHT&p=D&yr=2&mn=0&dy=0&id=p98578052474
Cool.
Time for action. Should be a big day.
odd trade: Pre-Market: 11.60 2.82 (19.56%) 6:09AM EST
Thanks, I saw 7.50 too, after I posted 11 or 12.
Just funny that the first time in months that I decide to look up max pain, and it's a whopping 6$ away.
Lookin strong now. Guess weekend buyout vig has set in.
some of those shorts are done covering and other vultures are running in now that market is turning...those vultures watched the shorts die and rot, they know the shorts are off the bid now and they see money to be made by steering twards max pain... I haven't looked up max pain in a long time... I bet it is around 12 or so.
any blip up will be sold, i think.
LMFAOROTFL wow that's cool
I like $12.30 and $11.61
january effect is over, this stock is so pretty and did fill a lot of those intraday gaps from last year's climb to 13.50 by plummeting to 7s... it would look much better going forward to abruplty test old trendlines.
so is "new 52week high" effect... the market is going to retest 200smas. but new 52 week highs will recur a few more times this year.
that angluar support needs testing from time to time... the slanted blue line... that old neckline that finally broke, but was agressively bought... that neckline projects forward into the future and it wants to be tested one or two more times.
A slanted look at another bunch of head and shoulders failures, and projecting forward with the old neckline... look how those necklines are support resistance later on. gold could have a huge run now that people are halfway through their january stock buying spree and OEX comes into play for the late-to-the-party.
I could see it trying to tap that orange line in two weeks.
Head and shoulders. sorry i put so many lines on this chart. don't know if ill have time to make a cleaner one. i think gold broke a neckline of a radically slanted head and shoulders and the price has fully tested support levels. all of the markets are waiting for some one to have more QE and for someone to say it out loud.
I looked at his list today and I see he posted yesterday, presumably a retort to the gecko article.
I can't read it though.
I wonder if he has a different interpretation of the hypertension stuff.
I think the non-accelerated approval and non-advisory meeting are bearish in that they mean cort will have to do more trials.
I have no shares left that I know of and am not short.
cort is hurting.
Yes it is very good to see light volume on a retreat... the heavy buyers were doing the work last 4 days and now in cruise control waiting for mince-able words from CEO. smells like they will sell the "no news" and it will recover in time for another build and sell off for the "no news" earnings report in feb.
cool... good start... that could end up being a life changer.
I sold covered calls yesterday on 1,000 shares
http://investorshub.advfn.com/boards/read_msg.aspx?message_id=70668028
and sold about 350 shares today
used funds to add to other positions.
that pretty much means I sold about 12% and loaned about 25%
Someone doesn't want to pay a penny higher than 1.19 this morning.
the run is almost over now that the broad market ($compq) has retested and confirmed over the 200sma. one more test of it to come though.
ARIA was a strong January leader so it broke new highs on this run and ARIA will pull back before the rest of the market gets tired today or tomorrow.
cap our gains the easy way.