Auxilium stated today that results from the "outside of plaque" animal trials should be available first half of 2008. Even so, the trials for Dupuytrens are to go ahead this year. They claim a success rate of 70% for Dupuytrens with a single 1/4cc injection of XIAFLEX. (3 doses maximum for Dupuytrens) When trials for Peyronie's restarts it may be 6 doses over about a 13 week period.

I just wanted to throw my 2 cents in and say that I am extremely excited about the Xiaflex results thus far. It is hard to be patient but the fact that it has made it to a second phase II trial is good news for all of us. We would not want for this process to be rushed so that we lose this promising treatment altogether!

What I hope for in the future is a treatment such as Xiaflex to address established fibrosis and a preventive treatment targeting the pathogenesis of the disease. Scientific knowledge expands exponentially, and with the biomedical techniques available today being applied to novel medical problems, I have to imagine that we could see this problem solved within 20 years. While that won't be as much help to some of us as others, at least guys in the future wouldn't have to deal with a problem like this because it is awful!

It is promising as well that there are other fibrotic conditions, such as pulmonary fibrosis, that are being researched. Medical therapy aimed at these conditions might produce a treatment that could be adapted for Peyronies Disease treatment. Further, as motivated as our country is to find the fountain of youth I imagine anyone who could find a pharmacologic means to stimulate production of elastin and reduce fibrosis and degradation of elastic tissue would be able to retire at a pretty early age! Don't think there are not people out there working on this day and night! Again, even if their target is skin integrity, low back pain...whatever it is...it may also have efficacy in our condition.

Just a few thoughts...everyone hang in there!

Found this in an emedicine article discussing Dupuytren's...at least demonstrates that there is thought going into prevention as well as treatment:

"Myofibroblasts are the primary cell type in Dupuytren disease and 5-fluorouracil (5-FU) inhibits both proliferation and myofibroblast differentiation in Dupuytren cell culture. Thus, 5-FU has the potential of being used as an adjuvant to reduce the rate of recurrence and contracture (Bansal, 2005)."

Now, that is a chemotherapeutic agent so not sure how feasible it would be to use something like this but who knows?

Does this relate to Peyronies Disease?




Protein Reverses Effects of Cardiac Fibrosis
Jul 30 2007, 11:47 AM EST
GEN News Highlights


Researchers at Beth Israel Deaconess Medical Center (BIDMC) further elucidated the origins of cardiac fibrosis, a scarring of the heart tissue that leads to a variety of cardiac diseases, most notably heart failure. The study also demonstrated that a molecule known as recombinant human bone morphogenic protein 7 (rhBMP7) can reverse the cardiac fibrosis process.

Fibrosis develops when the body's natural wound-healing process goes awry. Under normal conditions, specialized cells known as fibroblasts deposit layers of collagen protein to form a scar and thereby enable wounds to heal. However, in abnormal circumstances and for unknown reasons, excessive production of matrix proteins such as collagen, results in pathological scarring or fibrosis.

The researchers speculated that a specialized form of epithelial-mesenchymal transition known as endothelial-mesenchymal transition (EndMT) might be the mechanism behind this, so using knockout mice in which endothelial cells had been marked genetically, the investigators confirmed that, during cardiac fibrosis, these cells were indeed converting into activated fibroblasts that were depositing scar material and impeding the proper function and electrical conduction of the heart.

In the second part of the study, the investigators turned to the rhBMP7 protein to determine if it could successfully reverse the EndMT process in mice, reducing the development of fibroblasts and improving heart function.

"The rhBMP-7 protein was quite impressive in its ability to recover the function of damaged hearts," says Raghu Kalluri, Ph.D., senior author and chief of the division of matrix biology at BIDMC. "These findings provide compelling proof that the process of fibrosis can be reversed in the heart and offers the possibility of new therapies for patients who have developed cardiac fibrosis as the result of myocardial infarction, hypertension, valvular diseases, or heart transplantation."

The study appears in the July 29 advance online publication of Nature Medicine.

Source:  http://www.genengnews.com/news/bnitem.aspx?name=21011920

Liam, this is a really, really, good find.  And what was REALLY fascinating to me about it is that this is not the first time I have seen BMP7 mentioned in connection with fibrosis.  In fact I am trying to dig it out right now, I know I have it around here somewhere.  Well, it was research speculating that it would be useful in treating kidney disease and I have it on one of my computers somewhere and can't find it OR the hard copy.  But thats OK since good old Wikipedia actually references the latest on this with their BMP article:

QuoteBMP-7 has also recently found use in the treatment of chronic kidney disease (CKD). BMP-7 has been shown in murine animal models to reverse the loss of glomeruli due to sclerosis. Curis has been in the forefront of developing BMP-7 for this use. In 2002, Curis licensed BMP-7 to Ortho Biotech Products, a subsidiary of Johnson & Johnson.

http://en.wikipedia.org/wiki/Bone_morphogenetic_protein

So there you have it.  BMP-7 being used to treat kidney "sclerosis".  For those who might be in the dark, sclerosis is really just yet another term for fibrosis.  Plaque, scar tissue, sclerosis, its all just varying forms of fibrosis.  So if BMP-7 is useful in treating fibrosis of the heart AND fibrosis of the kidney, what other types of fibrosis might respond to it?  Fibrosis of the TA perhaps?  Hmmm ...

Another interesting point from the very same article:

QuoteOriginally, seven such proteins were discovered. Of these, six of them (BMP2 through BMP7) belong to the Transforming growth factor beta superfamily of proteins.  Since then, nine more BMPs have been discovered, bringing the total to sixteen.

Anybody notice anything curious about this statement?  It seems that BMP7 is DIRECTLY related to TGF-beta.  Such a coincidence.  And could it be that it actually is the perfect agent to turn TGF-beta-1 "off"?  - George

PS - I REPEAT ... This is the best time in history to have Peyronies!  With all the fibrosis research going on there WILL be a breakthrough soon.  Hang in there guys.  We are oh so close.  Don't let the stuff that doesn't pan out discourage you, there is more on the way.  We just have to be as pro-active as possible, encourage each other to see the bright side (and there really is a very bright side), and be informed so that we can have access to the best treatments as they emerge.

George,

The key word to me is reversed as opposed to stopped.  Many of our Peyronies Disease progressions have stopped or are inactive.  Reversal of the process is what seems so promising (yet still far away).  Who knows?

 Here is the abstract of the study George mentioned.



Articles by Morrissey, J.  
Articles by Klahr, S.  
Articles citing this Article  
Search for Related Content  

PubMed

PubMed Citation  
Articles by Morrissey, J.  
Articles by Klahr, S.  

J Am Soc Nephrol 13:S14-S21, 2002
© 2002 American Society of Nephrology

--------------------------------------------------------------------------------

Pathophysiology of Chronic Renal Failure and Complications

Bone Morphogenetic Protein-7 Improves Renal Fibrosis and Accelerates the Return of Renal Function
Jeremiah Morrissey*, Keith Hruska*, Guangjie Guo*, Song Wang*, Qing Chen* and Saulo Klahr*
Renal Division, *Department of Internal Medicine and Department of Cell Biology and Physiology, Washington University School of Medicine at Barnes-Jewish Hospital, St. Louis, Missouri.


Correspondence to Dr. Saulo Klahr, Department of Medicine, Barnes-Jewish Hospital (North Campus), 216 South Kingshighway Boulevard, St. Louis, MO 63110-1092. Phone: 314-454-7107; Fax: 314-454-5110; E-mail: [email protected]

Abstract

ABSTRACT. A prevention protocol has demonstrated that bone morphogenetic protein-7 (BMP-7) blunted the development of fibrosis in a rat model of unilateral ureteral obstruction. This prevention protocol also preserved, to an extent, renal function. The prevention protocol was extended and a treatment protocol used to examine if BMP-7 was beneficial at limiting fibrosis of the kidney when the BMP-7 was administered during the progression of fibrotic disease. Animals were distributed into four groups. Group 1 received vehicle, group 2 received enalapril (12.5 mg/kg body wt per d), group 3 received BMP-7 (50 or 300 µg/kg), and group 4 received both the enalapril and the high dose of BMP-7. Rats underwent reversible unilateral ureteral obstruction for 3 d, after which the obstruction was relieved. In the treatment protocol, 300 µg/kg BMP-7 was given after the release of obstruction. Seven days after release of the obstruction and the onset of treatment glomerular filtration rate (GFR), renal blood flow, and various histologic indexes of fibrosis were determined. On a consistent basis, BMP-7 treatment alone was found to be slightly but significantly (P < 0.04 to 0.007) better than enalapril alone or in combination with enalapril at decreasing interstitial volume or tubule atrophy. BMP-7 treatment was slightly but not significantly better (P < 0.09) than enalapril at restoring GFR in the prevention protocol. Treatment with BMP-7 significantly boosted GFR (P < 0.01) above that seen with vehicle treatment. These results suggest that BMP-7 treatment is capable of blunting the progression of fibrotic disease and of decreasing interstitial volume. Importantly, a return of renal function is accelerated by BMP-7 treatment. These results suggest that administration of BMP-7 may be an effective treatment to restore or preserve renal histology and renal function in this experimental model of renal disease.

http://jasn.asnjournals.org/cgi/content/abstract/13/suppl_1/S14

I decided this is the appropriate topic for these.

http://gut.bmj.com/cgi/content/abstract/56/5/706  - Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6VJ0-4N8164H-1G&_user=10&_coverDate=03%2F31%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=30cd508329bff5f75e0e797532785874 -The Effects of Rapamycin in the Progression of Renal Fibrosis

------------------------------------------------------------------------------------------------------------------------------------
Papers In Press, published online ahead of print June 11, 2007
J. Biol. Chem, 10.1074/jbc.M700194200
Submitted on January 8, 2007
Revised on June 6, 2007
Accepted on June 11, 2007


Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition
Michael Zeisberg, Changqing Yang, Margot Martino, Michael Duncan, Florian Rieder, Harikrishna Tanjore, and Raghu Kalluri
Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215

Corresponding Author: [email protected]

Activated fibroblasts are key contributors to the fibrotic extracellular matrix accumulation during liver fibrosis. The origin of such fibroblasts is still debated, although several studies point to stellate cells as the principal source. The role of adult hepatocytes as contributors to the accumulation of fibroblasts in the fibrotic liver is yet undetermined. Here we provide evidence that the pro-fibrotic growth factor, TGF-beta1, induces adult mouse hepatocytes to undergo phenotypic and functional changes typical of epithelial-to-mesenchymal transition (EMT). We perform lineage-tracing experiments using AlbCre.R26RstoplacZ double transgenic mice to demonstrate that hepatocytes which undergo EMT contribute substantially to the population of FSP1-positive fibroblasts in CCL4-induced liver fibrosis. Furthermore, we demonstrate that bone morphogenic protein-7 (BMP7), a member of the TGFbeta superfamily which is known to antagonize TGFbeta signaling, significantly inhibits progression of liver fibrosis in these mice. BMP-7 treatment abolishes EMT-derived fibroblasts, suggesting that the therapeutic effect of BMP7 was at least partially via inhibition of EMT. These results provide direct evidence for the functional involvement of adult hepatocytes in the accumulation of activated fibroblasts in the fibrotic liver. Furthermore, our findings suggest that EMT is a promising therapeutic target for the attenuation of liver fibrosis.

Source:  http://www.jbc.org/cgi/content/abstract/M700194200v1

------------------------------------------------------------------------------------------------------------------------------
Here's a repeat from a different source:

A new injectable mixed collagenase (AA4500, Auxilium Pharmaceuticals) was studied in two 12-month open-label studies to determine reduction in penile curvature and improvement of sexual quality of life in men with Peyronies Disease. Results from the studies were pooled for analysis (n = 35).[9] In both studies, sets of 3 injections over 7-10 days were given in different sequences over 6-12 weeks. At 9 months, 89% of patients had achieved clinical success; baseline angle of deviation improved by a mean of about 25°, all had pain-free erections, and other distressing physical symptoms improved. The size of the plaque, however, did not change significantly. Local adverse effects related to the injections did occur, but there were no generalized problems. Larger controlled trials are planned.

Source:  http://www.medscape.com/viewarticle/559060

roadblock, an English reconstructive surgery group called the Raft Institute tried 5-flourouracil on Dupuytren's several years ago, but did not see an effect.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6WJM-4BFX2KS-8&_user=10&_coverDate=02%2F29%2F2004&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=4cf406ea50f3ab4f1ef988161ae57339

Well Liam, here is another fascinating one:

QuoteBone morphogenetic protein-7 signals opposing transforming growth factor beta in mesangial cells.
Wang S, Hirschberg R.

Harbor-UCLA Research and Education Institute, UCLA, Torrance, California 90502, USA.

Bone morphogenetic protein-7 (BMP7) is expressed in adult kidney and reduces renal fibrogenesis when given exogenously to rodents with experimental chronic nephropathies. In mesangial cells that regulate glomerular fibrosis in vivo, BMP7 inhibits transforming growth factor beta (TGF-beta)-driven fibrogenesis, primarily by preventing the TGF-beta-dependent down-regulation of matrix degradation and up-regulation of PAI-1. The signals and mechanisms of the BMP7 opposition to actions of TGF-beta are unknown. Here we show in mesangial cells that BMP7 reduces nuclear accumulation of Smad3 and blocks the transcriptional up-regulation of the TGF-beta/Smad3 target, CAGA-lux. Smad5 knock-down impairs the ability of BMP7 to interfere with the activation of CAGA-lux and the accumulation of PAI-1 by TGF-beta indicating that Smad5 is required. Smad5 knock-down also reduces the rise in Smad6 upon BMP7. Forced expression of smad5 (found to be the preferred BMP7-induced receptor-activated Smad signal in mesangial cells) or of smad6 mimics BMP7 in opposing the increase in transcriptional activation of PAI-1 and its secretion upon TGF-beta. This suggests a model for the BMP7-induced opposition to TGF-beta-dependent mesangial fibrogenesis requiring Smad5; the model involves the inhibitory Smad6 downstream of Smad5 as well as reduced availability of Smad3 in the nucleus. BMP7 does not require signaling through Erk1/2, p38, or JNK and does not utilize the TGF-beta transcriptional co-repressors Ski or SnoN in mesangial cells. These studies provide first insights into mechanisms through which BMP7 opposes TGF-beta-induced glomerular fibrogenesis.

PMID: 15047707 [PubMed - indexed for MEDLINE]

- George

Trichostatin A prevents the accumulation of extracellular matrix in a mouse model of bleomycin-induced skin fibrosis.
http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17665426&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

Inhibition of TGF-beta induced lung fibroblast to myofibroblast conversion by phosphodiesterase inhibiting drugs and activators of soluble guanylyl cyclase.

http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17659276&ordinalpos=42&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

QuoteA new injectable mixed collagenase (AA4500, Auxilium Pharmaceuticals) was studied in two 12-month open-label studies to determine reduction in penile curvature and improvement of sexual quality of life in men with Peyronies Disease. Results from the studies were pooled for analysis (n = 35).[9] In both studies, sets of 3 injections over 7-10 days were given in different sequences over 6-12 weeks. At 9 months, 89% of patients had achieved clinical success; baseline angle of deviation improved by a mean of about 25°, all had pain-free erections, and other distressing physical symptoms improved. The size of the plaque, however, did not change significantly. Local adverse effects related to the injections did occur, but there were no generalized problems. Larger controlled trials are planned.

Source:  http://www.medscape.com/viewarticle/559060  Free registration.

Yes, I'm quoting myself.  Does any one have a direct link to the results?  

This report is giving me problems on so many levels.  On the surface it is very promising.  I am hopeful.  But that skeptic in me asks the questions.  If they are using collogenase, why didn't the plaque "breakdown"?  If the average was 25 degrees improvement, what was the range?

I would (and my name is in the pot) volunteer as a subject in the trials.  This report just made me pause.

http://ir.auxilium.com/phoenix.zhtml?c=142125&p=irol-eventDetails&EventId=1599870

I wonder if posts about developmental cures and research on associated disorders, should be posted under Developmental drugs and treatments - (Still in trial or not approved for Peyronies Disease)  

We have discussed fibrotic conditions like Dupuytrens Contracture, fibrosis of the heart, kidney fibrosis, just to name a few.  They all have related issues such as inflammation, and most mention TGF-B1.

Well, I was just doing a fast look-up on Cirrhosis of the liver for a friend.  I was interested when it said that it was caused by an inflammatory reaction that resulted in the progressive formation of fibrotic scar tissue that interferes with normal liver function.  I was startled however when it indicated that one of the many symptoms or associated complications is Dupuytrens Contracture.

The picture becomes more and more clear that most if not all fibrotic conditions seem to have clear common components.  Also, inflammation seems to be the root of an incredible range of disorders from vascular disease to cancer.  While this gives some hope, we cannot wait while a yet undiscovered cure for some associated fibrotic condition trickles down to us.  Between the discovery and the trickle it will be a long wait.  We need Peyronies Disease specific research.

Hawk, I think you are absolutely right.  The "Open Questions" and "General Comments" areas are notorious for drifting along and then, seemingly without warning, drifting over into one of the previously designated topic areas and focusing on it.  This seems to happen when such a subject gets gently touched on and others of us dive in and share our knowledge/discoveries/thoughts on the same subject.  This is when it becomes necessary for you (or Liam) to come along and move the specific clump of posts, like intruding weeds, into the proper pot.  Thanks for being so vigilant and picking up on our wayward ways.  - George

Ok, accuse me of being a bit slow.  To others this may be Peyronies Disease 101.  I only wish I had a lightbulb smiley.

Transforming Growth Factor - Beta 1 (TGF-B1) is a component of the immune system which I think is produced by smooth muscles under certain circumstances. One of its roles is to produce collagen.  I have long known that (TFG-B1) plays a role in the development of the fibrosis we know as Peyronies Disease.  As I began to learn more however, it is as though all the pieces are falling together.  It is as though everything revolves around TFG-B1.  This is what I think I know.

TGF-B1 is a key and possibly THE key that triggers Peyronies Disease fibrosis
Every non-surgical treatment suspected of working on Peyronies, seems to mediate (reduce) the production of TGF-B1    
         Pentox - thins blood and changes blood cell shape and also mediates TGF
         Viagra - Oxygenates the penis with blood, reducing the TGF produced by the smooth muscles.
         Now we just learned that the stretching by the VED somehow mediates TGF (not to mention mediation of TGF by any oxygenation) (lending more credibility to the VED)

Under the interesting topic "A New Theory" the writer has what seems like a well founded theory on the fibrosis of DC and Peyronies Disease based on insulin resistance.  The author was articulate but seemingly in left field as far as other theories were concerned.  Now, lo and behold I find out that (TGF-beta1) is a key regulator in inflammation and fibrosis in diabetes mellitus (I didn't know diabetes even involved fibrosis).  Every bit of this I have learned from members directly, or from Pub Med links that members posted.  Unless I am miscounting as I try to connect the dots this lends great credibility to this "New Theory" topic

TGF is at least related to Peyronies fibrosis, Heart Fibrosis, Dupuytrens Contracture fibrosis (DC), Cirrhosis of the liver fibrosis, and diabetes fibrosis.  

Cirrhosis is related to DC.  Peyronies is related to DC.  Peyronies is related to diabetes.

Why do older men tend to get Peyronies Disease and why do frequent erections tend to help?  It appears that reduction of oxygen in the penis from fewer erections causes the smooth muscles to produce TGF

I realize this has all been said more concisely and that i left out a lot of details but it increasingly looks like anything that helps Peyronies Disease does so only because it somehow mediates TGF.  Anything that is known to worsen Peyronies Disease does so only because it encourages the production of TGF.

Too simplistic

Do Peyronies Disease docs like Levine keep careful watch for other TGF fibrosis conditions, treatment, and research

What can we do to make people more aware we are here and that we also need direct Peyronies Disease related research on these issues

Hawk,

Looks like an amazing correlation's been developed between TGF-B1 and Peyronies Disease!  I'd suggest that your take your post and forward a copy of it to Levine and other top Peyronies Disease docs to a)get their opinion on the relationship between fibrosis and TGF or b)get them thinking about the relationship!  I'd love to hear their opinions.

Steve

Steve,

Let me explain my hesitation to do as you suggested.  First, I think TGF-B1 clearly is a key factor but the more basic problem may be what triggered its production.  Apparently each fibrotic condition has its own triggers that may only produce TGF-B1 in their respective tissue (I know little about this).  maybe we will never find a general TGF-B1 solution.  I am also completely unsure of whether other fibrotic diseases systemically flood the body with TGF-B1 or only the effected organ such as the liver in cases of cirrhosis.  Finely, I suspect it would take a doctor that was very:

Uninformed about TGF-B1
Exceptionally interested in research
And VERY VERY humble to accept anything I would point out or suggest.

As I learn more I may reconsider your suggestion since it costs nothing but rejection and I am highly experienced at dealing with that.  

It seems clear there is a connection. But, the actual chain of cause-and-effect may be so complex - and TGF-B1 may play so many roles in our biochemistry - that a way to manage this connection to our benefit may be far off.  We all realize it's unlikely that we'll really solve this problem by reading abstracts on the net.  BUT - if we cast a wide net, and monitor what's being done with related fibrotic conditions - we may eventually hear about something that works, long before it would be formally adopted by the urological 'community'.

Hawk,

Great summery!

J,

Couldn't agree more


One point I want to make is our comments here may actually influence the research community.  I cannot imagine researchers do not peruse this site from time to time.  What we talk about must be considered by the reader, even if it is only informally.  I'm not giving our site too much credit.  However, we are a respectable forum with a significant web presence (THANKS HAWK).  Don't think we may not have at least some impact.

J,

I always carefully read your posts because I can count on you for sound analytical comments.

Quote from: j on August 05, 2007, 02:46:14 PM
It seems clear there is a connection. But, the actual chain of cause-and-effect may be so complex - and TGF-B1 may play so many roles in our biochemistry - that a way to manage this connection to our benefit may be far off.  

I completely agree with this statement and I agree that it is only a small piece of the puzzle.  I also would be surprised if researches of Peyronies Disease and/or Peyronies Disease experienced urologists have not put all of this together before (although not real surprised).

I do scratch my head at the "speculation" part of your subject line.  I would have no pause at terms like "too simplistic", "incomplete", "shallow", but I can find no place it the post that I made a statement that is not pretty well established beyond the point of speculation.  If so, I want to correct it.  I may be a little over enthusiastic because a light (however dim) just clicked on.  

I did qualify a couple statements that have not been demonstrated beyond speculation with terms like "appears"

Hawk,  if you were speaking at a scientifc conference and laid out your case for TGF-B1, I t think there would be a lot of nodding but the term 'speculation' would still be heard.  From a lay person's point of view, there's a lot of solid evidence and the connection seems beyond question; in a formal academic setting I think the idea would still be termed "speculative" until proven by experiment.

J, I think if I were to speak at a scientific conference that there would be a tar and feathering going on  

I think if you spoke at a urological convention, there would be a lot of embarassed silence as doctors realized how little they know about this condition that they probably see every week, compared to how much one can learn with a couple hours of Googling.

Hi guys...
just a quick note...I found one description for Vitamin E in the Slovakian
Database of Drugs and was very suprised that they admit Vit E as a
therapy for Induration Penis Plastica, also they say how much of it a man
must take to treat it ...even there is no approved clinical study for it, you know..
Here is the link if you want to look:

http://www.sukl.sk/buxus/docs/download/vitamin_e_100_200_400_cps_spc.pdf

if it doesnt work, try this one
http://www.sukl.sk/sk/pomocne-stranky/detail-lieku?lie_id=52716
and click on the first hypertext below.

Its in Slovakian but on the first page there is expression "Plasticka induracia penisu" (its IPP)
in the "4.1 Therapeutic indications" chapter.
And also "Iduratio Penis Plastica" on the second page in the "4.2 Measurment and aplication"
They say, you should take 300-400 mg daily during a few weeks and then 50 mg daily during a
few months.

I will be back soon with an update of my condition. I am going to have a few appointments with
urologists soon.

But I read all new posts everyday, and its always very interesting reading.

R3

Developing gene therapy vectors for therapeutic uses in urology:

I take it that people have seen this already: http://www.cdrewu.edu/cosh/biomedical_sciences/mcgee.htm

If so, apologize for the repost.

McGee has worked with Gonzalez-Cadavid, who is a leader in Peyronie's research.

Tim

QuoteGene transfer of inducible nitric oxide synthase complementary DNA regresses the fibrotic plaque in an animal model of Peyronie's disease.Davila HH, Magee TR, Vernet D, Rajfer J, Gonzalez-Cadavid NF.
Department of Urology, UCLA School of Medicine, Los Angeles, California 90095, USA.

The goal of the present study was to investigate the antifibrotic role of inducible nitric oxide synthase (iNOS) in Peyronie's disease (Peyronies Disease) by determining whether a plasmid expressing iNOS (piNOS) injected into a Peyronies Disease-like plaque can induce regression of the plaque. A Peyronies Disease-like plaque was induced with fibrin in the penile tunica albuginea of mice and then injected with a luciferase-expressing plasmid (pLuc), either alone or with piNOS, following luciferase expression in vivo by bioluminescence imaging. Rats were treated with either piNOS, an empty control plasmid (pC), or saline. Other groups were treated with pC or piNOS, in the absence of fibrin. Tissue sections were stained for collagen, transforming growth factor (TGF) beta1, and plasminogen-activator inhibitor (PAI-1) as profibrotic factors; copper-zinc superoxide dismutase (CuZn SOD) as scavenger of reactive oxygen species (ROS); and nitrotyrosine to detect nitric oxide reaction with ROS. Quantitative image analysis was applied. Both iNOS and xanthine oxido-reductase (XOR; oxidative stress) were estimated by Western blot analysis. Luciferase reporter expression was restricted to the penis, peaked at 3 days after injection, but continued for at least 3 wk. In rats receiving piNOS, iNOS expression also peaked at 3 days, but expression decreased at the end of treatment, when a considerable reduction of plaque size occurred. Protein nitrotyrosine, XOR, and CuZn SOD increased, and TGFbeta1 and PAI-1 decreased. The piNOS gene transfer regressed the Peyronies Disease plaque and expression of profibrotic factors, supporting the view that endogenous iNOS induction in Peyronies Disease is defense mechanism by the tissue against fibrosis.

PMID: 15240426 [PubMed - indexed for MEDLINE]

Source:  http://www.ncbi.nlm.nih.gov/sites/entrezcmd=Retrieve&db=pubmed&dopt=AbstractPlus&list_uids=15240426

It's an older paper - once again out of the lab of Gonzalez-Cadavid. See the pattern? Almost all of the original thought in this field seems to come from him and his trainees or collaborators.

Unfortunately, he's a PhD, so I can't go see him for a consultation.

Tim

Auxilium announced 2 days ago that the FDA has given them clearance to resume Phase III clinical trials of XIAFLEX for Dupuytrens. This approval came earlier than expected. Enrollment of 725 patients expected to begin within 30 days. Trials to be conducted in U.S. & Australia. As you may recall the 2006 trial was interrupted when it was discovered that some of the vials of collagenase had too much moisture in them (melt back). It is great to know that Auxilium has solved this manufacturing problem. Also, the FDA has lifted the "clinical hold" on XIAFLEX for use with Peyronie's. The next step is for out of plaque animal studies to be completed so that XIAFLEX trials for Peyronie's can begin.

Mark,

Thanks for the update, this is some positive news.  I'm looking forward to seeing some more trial results sometime soon.  Specifically I'm looking forward to reports with more details than we saw last time.  Hopefully once good dupuytrens results come back they will finally start using xiaflex off label for peyronies disease.  Keep us updated, and if anyone knows of any local trial opportunities, don't hesitate to inform us.  I know before blink let us know, I put my name on a list, haven't heard anything from auxillium since then.

Comeback

As stated above if the drug is approved for another use it can be used off label for Peyronies Disease.  Insurance carriers wont pay but so be it if it works.  Personally I am waiting for the results of the animal studies before I rush into being a trial subject.

Just one comment.  Insurance often pays for off label use.  It may be because the doctor writes it up differently to make it look like it is NOT off label.  If this is true I guess it would be difficult in this case unless he could declare that you have Dupuytren's Contracture of the penis.  

Maybe he could be creatively deceptive with the vague diagnose of Dupuytren's Contracture of one of the patient's digits.

I have progressive Dupuytren's in both hands.  So if and when this stuff becomes real, I'll find a hand surgeon who's using it;  and when I get the treatment, I'll pull out $1,000 in small bills and ask if he'll inject me in a couple of other spots.  Ok I'm kidding.

 You're right - flourouracil does not work.  

Hi Colleen,  Do you have experience with flouroucil?  Please share.  

With a big Celtic welcome,
Liam

Is this something that could reverse payronie's?

http://www.intercytex.com/icx/products/woundcare/icxskn/

http://ir.auxilium.com/phoenix.zhtml?c=142125&p=irol-newsArticle&ID=1050270&highlight=

Quote from: Franklins Tower on September 10, 2007, 02:03:50 PM
Is this something that could reverse payronie's?

http://www.intercytex.com/icx/products/woundcare/icxskn/

Nope.

Tim

FT, We have all been anxiously awaiting completion of the "Xiaflex" (collegenase) study.  I am cautiously optimistic.

Liam

anyone know when they are planning to start the IIB studies in Peyronies Disease.  Did the dog study ever happen?

FYI:

QuoteAuxilium Pharmaceuticals, Inc. (NASDAQ: AUXL) will webcast its analyst and institutional investor meeting to be held at the Grand Hyatt Hotel, on Park Avenue at Grand Central, in New York City on Wednesday, October 17, 2007.

The event will feature a discussion of clinical data and potential future commercial opportunities for XIAFLEX(TM), the Company's lead pipeline candidate that is currently in phase III development for the treatment of Dupuytren's contracture and in phase II development for the treatment of Peyronie's disease. Participants from Auxilium will include Mr. Armando Anido, Chief Executive Officer and President, Mr. Jim Fickenscher, Chief Financial Officer, Mr. Roger Graham, Executive Vice President, Sales and Marketing, and Dr. Jyrki Mattila, Executive Vice President, Business Development, R&D, and Technical Operations. Speakers will include the following leading scientific experts in the treatment of Dupuytren's contracture and Peyronie's disease:


--  Lawrence Hurst, M.D., Professor and Chair, Chief of Hand Surgery,
   Department of Orthopaedics of the Health Science Center, State University
   of New York at Stony Brook
--  Gerald H. Jordan, M.D., F.A.C.S., F.A.A.P., Professor, Department of
   Urology, Eastern Virginia Medical School Director, Devine Center for
   Genitourinary Reconstructive Surgery, Sentara Norfolk General Hospital
   

The event will be held from 11:30 a.m. to 3:30 p.m. Eastern Time. To access the live web cast for the presentation, which will begin at 12:00 p.m. Eastern Time, please log on to the Company's web site at www.auxilium.com approximately 15 minutes prior to the presentation. The web cast will also be archived and available on the Company's web site approximately one hour after completion of the live web cast and will remain available for approximately 90 days after the event.

About Auxilium

Hi,

Will any one be listening to this meeting ?

I am very interested to hear what they have to say, but I will busy at work.

It's also going to be 'archived' at the company's website, and will be there for about 90 days for those of us who can't listen to it 'live'.

Check this out from Modern Marvels on The History Channel - It features Dr. Anthony Atala from Harvard aand promises to have these treatments available it 3 to 10 years.

http://www.history.com/media.do?action=clip&id=mm_hts_gene_therapy_broadband

Also on this show but not on this clip was Viagra that you rub on your penis.  If this direct application methond works it my cut down or eliminate the side effects

Hawk,

Do you mean that there will be ED product that is like HEAD ON - APPLY DIRECTLY TO THE FOREHEAD?

I suppose it will be called (sorry about this):   HARD ON - APPLY DIRECTLY TO THE FORESKIN  

Liam:

In our US TOO group we have several drug company reps that attend our meetings at various times. They even sponsor meals for us, etc. They keep us to speed on the development of new drugs for ED, prostate cancer and related men's health problems.

At least two of the companies have been or are in the process of developing, testing and getting FDA approval for a topical ED cream. MUSE (Male Urethral Suppository for Erections) is in the same family. MUSE is injected in the urethra and in a very short time an erection occurs. It does have a nasty side effect for some guys. It produces a severe burning sensation especially after intercourse, etc.

I am sure that in the near futurre, at least one of these medial producers will have a topical erection cream on the market.

OM

That's a pretty amazing clip, Hawk. I'll hope for the best but expect a lot of setbacks and problems (and a looooong time for it to become affordabile to the common man) until we get DNA-grown Peyronies Disease-free packages.

Sorry if this a bit off topic, but

Auxilium Pharmaceuticals, Inc. Completes Enrollment in Two Phase III Clinical Trials of XIAFLEX(TM) for Dupuytren's Contracture


MALVERN, PA, Dec 17, 2007 (MARKET WIRE via COMTEX News Network) -- Auxilium Pharmaceuticals, Inc. (NASDAQ: AUXL) today announced that it has completed patient enrollment in the Company's second U.S. phase III pivotal trial (CORD I) and its Australian phase III study (CORD II) of XIAFLEX(TM) (clostridial collagenase for injection) for the treatment of Dupuytren's contracture. In accordance with the study design, all enrolled patients have received their first injection of either XIAFLEX or placebo. Due to the high level of interest from patients and physicians, the Company was able to exceed its enrollment targets in both studies, with greater than 300 patients enrolled in the CORD I and CORD II studies combined. The Company had targeted enrolling 216 patients in CORD I and 60 patients in CORD II.  

Well it is not for peyronie yet, but I guess we are getting closer to a release of Xiaflex I think hope it will help us