Trials and Tribulations of Dr. Fasano

[Zonulin]

Has someone already posted this?? http://www.medicalnewstoday.com/medicalnews.php?newsid=52442

Karen

[2silverwings]

Yes I saw that - I'm also very hesitant to get too excited about it until it's fully tested and FDA approved. It might be helpful for avoiding cross-contamination especially. LIke someone on another board I'm on said, what celiac/gluten intolerant person would want to volunteer for this study?!?

[jcc]

Thanks, Karen!

I haven't seen this, I don't think. I know I saw the Alba announcement about Phase I. This is so interesting watch all these things happen as they happen.

Cara

[annelb]

Here is the cute animation about "tight junction dysfunction" and Zonulin.
http://www.albatherapeutics.com/science-technology/index.html
Anne

[annelb]

Hot off the press!

I think Dr. Fasano is sitting on a Zonulin test that will become available as
soon as his blocker is approved. Wonder how the Phase II trials are going?
Anne

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17053448&query_hl=8&itool=pubmed_docsum

Curr Opin Gastroenterol. 2006 Nov;22(6):674-9.
Systemic autoimmune disorders in celiac disease.

* Fasano A.

Center for Celiac Research and Mucosal Biology Research Center and Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.

PURPOSE OF REVIEW: Celiac disease is an immune-mediated disorder clinically characterized by a multitude of symptoms and complications. The comorbidity between celiac disease and other autoimmune disorders has been clearly established. RECENT FINDINGS: Two main theories have been postulated to explain this comorbidity: (1) linkage disequilibrium between the genes responsible for celiac disease and those responsible for the coexpressed autoimmune diseases or (2) untreated celiac disease leading to the onset of other autoimmune diseases. This article reviews the current literature supporting either theory and places the current knowledge in the field within the context of the most recent data on the pathogenesis of celiac disease. SUMMARY: The current literature did not clearly establish which of the two theories explain the comorbidity between celiac disease and other autoimmune disorders. There is, however, growing evidence that the loss of the intestinal barrier function typical of celiac disease could be responsible of the onset of other autoimmune disease. This concept implies that the autoimmune response can be theoretically stopped and perhaps reversed if the interplay between autoimmune predisposing genes and trigger(s) is prevented or eliminated by a prompt diagnosis and treatment.

PMID: 17053448 [PubMed - in process]

[diamondheart]

Hot off the press!

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17053448&query_hl=8&itool=pubmed_docsum

This looks like a great article. Thanks Anne! Do we have to wait to access it since it's a November article? Have you read the whole article?

Claire

[annelb]

This looks like a great article. Thanks Anne! Do we have to wait to access it since it's a November article? Have you read the whole article?

Claire

Haven't read it yet - will let you know if/when I get access.
Anne

[jcc]

Yep.... so more to come!

Great article! I had to file it a few places!

Cara

[Zonulin]

Here is the cute animation about "tight junction dysfunction" and Zonulin. -
Annelb Well, not CUTE - not for the kiddies, anyway ;) Getting a jump on that "November" publication date will be a feat. I continue to try to tell people that most autoimmune conditions revert back to too much Zonulin and wheat wreaking its damage throughout the body (including its ability to pass through the brain/blood barrier). Hard for people to "get" that an apparently "innocent" piece of wheat bread contains tissue-eating protein that can do a lot of damage when it is able to get outside the gastro tract. It's a hard sell...:eek: :rolleyes: Maybe a Pacman visual would help.

Meat-eater, no wheat-eater,
Karen

[annelb]

Well, not CUTE - not for the kiddies, anyway ;) Getting a jump on that "November" publication date will be a feat. I continue to try to tell people that most autoimmune conditions revert back to too much Zonulin and wheat wreaking its damage throughout the body (including its ability to pass through the brain/blood barrier). Hard for people to "get" that an apparently "innocent" piece of wheat bread contains tissue-eating protein that can do a lot of damage when it is able to get outside the gastro tract. It's a hard sell...:eek: :rolleyes: Maybe a Pacman visual would help.

Meat-eater, no wheat-eater,
Karen

Well, those little bouncing gliadins are sort of cute :rolleyes:

I guess all those people you tell about wheat bread don't really have to worry cause they eat white bread - white bread is made of .... ummmm.....white stuff :confused:
Anne

[NancyM]

Maybe someone can help me remember...

Wasn't it found that ingesting wheat opens the TJ's for everyone? But for celiacs they stayed open?

[annelb]

This is what you might be thinking of:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=16635908&query_hl=7&itool=pubmed_docsum

Scand J Gastroenterol. 2006 Apr;41(4):408-19.
Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines.

* Drago S,
* El Asmar R,
* Di Pierro M,
* Grazia Clemente M,
* Tripathi A,
* Sapone A,
* Thakar M,
* Iacono G,
* Carroccio A,
* D'Agate C,
* Not T,
* Zampini L,
* Catassi C,
* Fasano A.

Mucosal Biology Research Center, Center for Celiac Research and Division of Pediatric Gastroenterology and Nutrition, University of Maryland, School of Medicine, Baltimore, MD 21201, USA.

OBJECTIVE: Little is known about the interaction of gliadin with intestinal epithelial cells and the mechanism(s) through which gliadin crosses the intestinal epithelial barrier. We investigated whether gliadin has any immediate effect on zonulin release and signaling. MATERIAL AND METHODS: Both ex vivo human small intestines and intestinal cell monolayers were exposed to gliadin, and zonulin release and changes in paracellular permeability were monitored in the presence and absence of zonulin antagonism. Zonulin binding, cytoskeletal rearrangement, and zonula occludens-1 (ZO-1) redistribution were evaluated by immunofluorescence microscopy. Tight junction occludin and ZO-1 gene expression was evaluated by real-time polymerase chain reaction (PCR). RESULTS: When exposed to gliadin, zonulin receptor-positive IEC6 and Caco2 cells released zonulin in the cell medium with subsequent zonulin binding to the cell surface, rearrangement of the cell cytoskeleton, loss of occludin-ZO1 protein-protein interaction, and increased monolayer permeability. Pretreatment with the zonulin antagonist FZI/0 blocked these changes without affecting zonulin release. When exposed to luminal gliadin, intestinal biopsies from celiac patients in remission expressed a sustained luminal zonulin release and increase in intestinal permeability that was blocked by FZI/0 pretreatment. Conversely, biopsies from non-celiac patients demonstrated a limited, transient zonulin release which was paralleled by an increase in intestinal permeability that never reached the level of permeability seen in celiac disease (CD) tissues. Chronic gliadin exposure caused down-regulation of both ZO-1 and occludin gene expression. CONCLUSIONS: Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.

PMID: 16635908 [PubMed - indexed for MEDLINE]


How much zonulin release and how long does the gut need to be permeable to cause damage to the whole body? Is any amount too much?
Anne

[NancyM]

I was reading the Loren Cordain is going to publish something about epithelial cells and eating grains along with milk. Something about the combination of the two. I have no idea when that'll come out but it sure sounds interesting.

[annelb]

Dr. Alessio Fasano, a professor at the University of Maryland, Baltimore and co-founder of Baltimore's Alba Therapeutics Corp., was honored Monday with the university's first "entrepreneur of the year" award.

http://baltimore.bizjournals.com/baltimore/stories/2006/10/23/daily5.html?surround=lfn

Anne

[jcc]

I think Dr. Fasano is right up there in hero status with Dr. Hadjivassiliou, but whether or not an effective drug comes out of this, I think the far greater good will be if it becomes proven and universally accepted that leaky gut plays a role in other autoimmune disease and that "non-celiac" gluten (and casein) sensitivity is a real entity.

Cara

[Electra375]

I for one think Dr. Fasano is awsome even though I do not agree with drugs in general. Dr. Fasano was the only one willing to look at blood test and say my ds2 was IGA deficient and therefore the IGG that was so high was good enough for now. He holds the belief that if one has the CD genes and is IGA deficient with IGG positives -- it's a no brainer the person is likely Celiac. He asked me if I thought my ds2 had CD, of course I said yes and he said he was inclined to agree, but without a biopsy he could not put it in writing. He also agreed with me that waiting on a biopsy was in the best interest of my ds2 given his very ill health and by the time we got to see him ds2 was gf for 5 months with proven results of weight gain and height with over all health increasing. He told me waiting until age 10 would be fine.

He is a pioneer in his field and I'm thankful there are doctors like him who are smart and innovative.

[aklap]

I for one think Dr. Fasano is awsome even though I do not agree with drugs in general.
I've always wondered if there's not some conflict of interest somewhere along the way. Here's a doctor treating patients for CD...then the same doctor forming a company that is developing [& selling] a drug to treat said patients. Something about that relationship just seems odd to me. Maybe that's how drugs are made...I don't know.

[JudyLV]

I sort of agree with you Al. But it would be a shame to lose Dr. Fasano to the business side of the research. He has helped so many people. I think the drugs can only be developed by the person who has done the research. I am also against drugs when diet alone will do the trick but if his research could lead to helping stop or reverse other autoimmune diseases that would be great.

On another Dr. Fasano note. My 11 year old son and I were watching tv the other night. He is a real channel flipper and something came up on crop circles. I thought it was interesting and asked him to go back to it. He said he already knew all about them. I asked him what he knew and he said "I think they are made by Dr. Fasano because he doesn't want people to eat wheat."

--Judy

[jcc]

"I think they are made by Dr. Fasano because he doesn't want people to eat wheat."

That is pretty good!

:D :D :D

[annelb]

People with CD, people with autoimmune diseases and now dogs. Zonulin may be good for people and puppies. I copied the complete article as too often they disappear with time.

http://www.earthtimes.org/articles/show/news_press_release,12368.shtml

Alba Therapeutics Corporation and The Royal Veterinary College, London Announce Initiation of AT-1001 Study in Patient Dogs with Inflammatory Bowel Disease
Posted on : Mon, 30 Oct 2006 13:08:01 GMT | Author : Alba Therapeutics Corporation
News Category : PressRelease

BALTIMORE and LONDON, Oct. 30 /PRNewswire/ -- Alba Therapeutics Corporation (Alba) and The Royal Veterinary College, London (RVC) today announced that they have initiated a study in dogs stricken with Inflammatory Bowel Disease (IBD), to assess the use of Alba's zonulin receptor antagonist, AT-1001. The double-blinded, placebo-controlled and randomized study will enroll 60 IBD patient dogs presenting to The Queen Mother Hospital for Animals, RVC, in four arms and will assess the ability of AT-1001 to reduce the signs, clinical markers and histopathological lesions associated with IBD.

"We are extremely pleased to be working with the RVC in this important study," stated Dr. Blake Paterson, CEO of Alba Therapeutics. "While Alba continues to assess the use of zonulin antagonist, AT-1001, in validated IBD animal models, the ability to run a clinical trial in patient dogs will provide useful clinical insight and allow us greater confidence that zonulin receptor antagonism may offer advantages over conventional immunosuppressive and dietary measures in both dogs and humans. We are fortunate to be working with our RVC collaborators, as they are uniquely qualified to run this study as established leaders in the development and implementation of animal clinical trials."

Within each of the four arms of the clinical trial, patient dogs will receive a hydrolysed veterinary diet. In the first arm, patients will receive the diet and AT-1001 and in the second arm, patients will receive the diet, AT-1001 and prednisolone. In the third and fourth arms, patients will respectively receive the diet and placebo, or diet, placebo and prednisolone.

"We believe the potential clinical benefit of AT-1001 in diseases characterized by increased intestinal permeability such as IBD to be powerful," stated David Walker, lead Co-Investigator. "Alba's progress with AT-1001 in Celiac Disease, together with the scientific rationale supporting the use of zonulin receptor antagonism in inflammatory diseases, gives us great confidence that this study will open the door to other therapeutic applications for the product," stated Oliver Garden, Principal Investigator of the Canine IBD Clinical Trial.

IBD is an inflammatory disease that can involve either or both the small and large bowel and is often considered a disease of adolescents and young adults, because it is most commonly first diagnosed in people between the ages of 15 and 35 years. Active IBD is characterized by acute inflammation, whereas chronic IBD is characterized by architectural changes of crypt distortion and scarring. Crohn's disease and ulcerative colitis are the best-known forms of IBD. IBD is estimated to affect 1.4 million people in the United States and up to 2.2 million people in Europe.

About Alba: Alba Therapeutics is a Baltimore-based biopharmaceutical company dedicated to commercializing disease-modifying therapeutics and drug delivery adjuvants based on the zonulin pathway. Alba's lead product, AT-1001, is currently in a Phase II trial for Celiac Disease and is planned to enter clinical studies in Type 1 Diabetes in 2007 following an IND filing in late 2006. Alba is testing zonulin receptor antagonists, including AT-1001, in a variety of autoimmune and inflammatory diseases.

About RVC: The Royal Veterinary College (RVC) is the UK's first and largest veterinary school and a College of the University of London. Since its foundation in 1792, it has become a world-leader in veterinary and biomedical teaching and research. The Queen Mother Hospital for Animals is the largest small animal teaching hospital in Europe and leads the world in clinical trials of new and exciting diagnostic modalities and therapeutic agents. The Canine IBD Clinical Trial is being led by Oliver Garden, a veterinarian with over 13 years' experience in the fields of veterinary gastroenterology and immunology.

Alba Therapeutics Corporation




CD does not have a good animal model although animals do react to gluten. Sounds as though there is an increase of zonulin in the pups.
Anne

[annelb]

This was presented by Dr. Fasano at the International Celiac Symposium. Currently the Phase II trials are underway. This tests humans during a gluten challenge. Looks promising.

http://www.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/11-13-2006/0004472513&EDATE=

Alba Therapeutics Presents Data from Positive Phase Ib Clinical Trial at the XII International Celiac Disease Symposium

NEW YORK, Nov. 13 /PRNewswire/ -- Data presented on November 11th at
the XII International Celiac Disease Symposium in New York City show that
when AT- 1001, an investigational oral zonulin receptor antagonist being
developed for treatment of Celiac Disease ("CD"), was assessed in a double
blind, placebo controlled study of CD patients, the product induced a
positive result on the trial's primary endpoint, intestinal permeability.
The objective of the Phase Ib proof of concept study was to establish the
safety, tolerability and effectiveness of single doses of oral AT-1001 in
adult CD patients in remission that are challenged with a large dose of
gluten. Key findings from this Phase Ib study include:
* Intestinal barrier function was maintained by AT-1001 despite a
supramaximal stimulus with gluten. There was a significant increase in
permeability in placebo recipients but not in AT-1001 recipients following
the 2.5 gram gluten challenge, as determined by urinary
Lactulose-to-Mannitol (L- to-M) ratio.
* AT-1001 was generally safe and well tolerated, and no serious adverse
events were reported.
* AT-1001 plasma concentrations were unmeasureable (< 0.5 ng/ml),
indicating little to no systemic absorption when administered orally.
* The biological effect of AT-1001 persisted beyond the drugs residence
time, suggesting that AT-1001 modulates both persistent leak and immune
activation.
* Symptoms of acute gluten toxicity were inhibited in the AT-1001 arm
when compared to placebo.
"AT-1001's inhibitory effect is most likely related to its capacity to
prevent zonulin binding to its receptor on the lining of the gut, reducing
exposure to gliadin and immune activation," stated Blake Paterson, M.D.,
Alba's Co-founder and CEO. "We are excited by the demonstration of a
systemic immunological benefit arising from a physiological event at a
mucosal surface of the small bowel, and look forward to completion of our
Phase II clinical trial to further assess AT-1001's impact in this
debilitating disease."
About AT-1001
AT-1001 is an orally administered octapeptide zonulin receptor
antagonist that appears to exert its inhibitory effect on gliadin-induced
tight junction disassembly by blocking putative zonulin receptors on the
luminal surface of the small intestine. Pretreatment with the peptide fails
to inhibit gliadin induced zonulin release, while administration of zonulin
analogues or gliadin in the presence of AT-1001 fail to significantly
affect intestinal permeability, confirming the effect of the molecule is
specific to the zonulin receptor. AT-1001 is currently under investigation
in a multicenter, double blind, placebo controlled Phase II dose ranging
study to evaluate the safety, tolerability and efficacy of AT-1001 in 79 CD
subjects during gluten challenge.
About Zonulin
Zonulin is an endogenous signaling protein that transiently and
reversibly opens the tight junctions between the cells of epithelial and
endothelial tissues such as the intestinal mucosa, blood brain barrier and
pulmonary epithelia. Discovered by Alba's co-founder, Dr. Alessio Fasano,
zonulin appears to be involved in many disease states in which leakage
occurs via paracellular transport across epithelial and endothelial tight
junctions, and thus may play an important potential role in the treatment
of autoimmune and inflammatory diseases.
About Celiac Disease
Celiac disease is a T-cell mediated auto-immune disease that occurs in
genetically susceptible individuals and is characterized by small
intestinal inflammation, injury and intolerance to gluten. According to the
National Institutes of Health, CD affects approximately 3 million
Americans. The only current treatment for CD is complete elimination of
gluten from the diet, which results in remission for some patients.
About Alba
Alba Therapeutics Corporation is a privately held biopharmaceutical
company based in Baltimore, Maryland. Alba is dedicated to commercializing
disease-modifying therapeutics and vaccine and drug delivery adjuvants
based on the zonulin pathway. Alba's lead molecule, AT-1001, is targeted
towards the treatment of Celiac Disease and Type 1 Diabetes and other
autoimmune diseases.
Contact: Stuart Sedlack, SVP, Corporate Development
Phone: 410-319-0780
E-mail: info@albatherapeutics.com
Web site: http://www.albatherapeutics.com

[Zonulin]

Very fascinating, Anne - thanks for posting this! I was just thinking how Frankensteinien it was to change people's cell walls to accommodate gluten, but after reading this got to thinking about all the people who are suffering from an undiagosed or diagnosed autoimmune illness. If they are able to take this drug and improve their health without changing their diet, that is a good thing. Thousands if not millions of these people are NOT going to be told by their doctors that if they eliminate gluten, their health will improve. I've never met a doctor who was enthusiastic about the gluten-free diet. BUT doctors love to prescribe meds and patients love to see whether the meds will work for them...this could work!

How wonderful it would be to eliminate so much suffering for so many people. And the wheat industry won't have to suffer, either. ;) My family? We're sticking with the gluten-free diet (with the spectre of hereditary gastro cancers in our collective consciousness). But I say let those sufferers of fibromyalgia, M.S., diabetes, lupus, etc. (not to mention gluten sensitivity, which is never "diagnosed" and will continue to be overlooked) be given an easy tool to take back their good health and quality of life. The less suffering in this world, the better :D

LET THEM EAT CAKE!! :p

Karen jumping off her soapbox (whew)

[annelb]

Here is the latest news release from Alba. They seem to be coming with more frequency. The trials look promising and the money is coming in. Maybe we should get some Alba stock :confused: That would really be putting our money where are mouth is :rolleyes:

Alba Therapeutics Corporation Announces $10 Million in Financing



BALTIMORE, Nov. 27 /PRNewswire/ -- Alba Therapeutics Corporation
announced today that it secured a $10 million venture debt commitment from
a syndicate consisting of Atel Ventures, Inc., Oxford Finance Corporation
and SVB Silicon Valley Bank. This additional source of capital will enable
the company to accelerate the clinical development of AT-1001 in celiac
disease and other autoimmune indications during 2007.
AT-1001 is an orally administered zonulin receptor antagonist that is
currently under investigation in a multicenter, double blind, placebo
controlled Phase II dose ranging study to evaluate the safety, tolerability
and efficacy of AT-1001 in 79 CD subjects during gluten challenge.
"The promising clinical and preclinical data generated with AT-1001 in
celiac disease and other autoimmune conditions warranted that we access
this capital in order to expedite activities supporting clinical trials,"
said Blake Paterson, M.D., Chief Executive Officer of Alba. "We now have
the ability to fast track the AT-1001 program to address the enormous unmet
needs of celiac patients and others suffering from autoimmune diseases."
About Celiac Disease
Celiac disease is a T-cell mediated auto-immune disease that occurs in
genetically susceptible individuals and is characterized by small
intestinal inflammation, injury and intolerance to gluten. According to the
National Institutes of Health, CD affects approximately 3 million
Americans. The only current treatment for CD is complete elimination of
gluten from the diet, which results in remission for some patients.
About Alba: Alba Therapeutics is a biopharmaceutical company dedicated
to discovering, developing and commercializing superior immunological
disease and inflammation therapeutics by leveraging our barrier function
technology platform delivering value to our patients, employees and
shareholders. Alba's platform, the zonulin pathway, provides the ability to
transiently and physiologically regulate tight junctions in cellular
barriers such as the intestinal mucosa and the pulmonary epithelia.
Modulation of paracellular permeability allows Alba to develop applications
ranging from therapies associated with tight junction dysfunction and
autoimmunity to vaccine and drug delivery. Alba's lead product, AT-1001, a
zonulin receptor antagonist, is currently in a Phase II trial for Celiac
Disease. Alba is testing AT-1001 and other antagonists in a variety of
autoimmune and inflammatory diseases and expects to enter clinical trials
in additional indications during 2007.
Contact: Stuart Sedlack, SVP, Corporate Development
Phone: 410-319-0780
E-mail: info@albatherapeutics.com
Web sites: http://www.albatherapeutics.com


SOURCE Alba Therapeutics Corporation

[NancyM]

I think it is a privately held company isn't it?

[annelb]

Here is the patent application for the Agonist polypeptide of receptor for zot and zonulin http://www.freshpatents.com/Agonist-polypeptide-of-receptor-for-zot-and-zonulin-dt20061207ptan20060276403.php?type=description

There is a link to a short version on this page.

This patent covers all forms of administration and testing for autoimmune disease. [0063] Antibodies to the zot/zonulin receptor can be used as anti-inflammatory agents for the treatment of gastrointestinal inflammation that gives rise to increased intestinal permeability. Thus, the antibodies of the present invention are useful, e.g., in the treatment of intestinal conditions that cause protein losing enteropathy. Protein losing enteropathy may arise due to: infection, e.g., C. difficile infection, enterocolitis, shigellosis, viral gastroenteritis, parasite infestation, bacterial overgrowth, Whipple's disease; diseases with mucosal erosion or ulcerations, e.g., gastritis, gastric cancer, collagenous colitis, inflammatory bowel disease; diseases marked by lymphatic obstruction, e.g., congenital intestinal lymphangiectasia, sarcoidosis-lymphoma, mesenteric tuberculosis, and after surgical correction of congenital heart disease with Fontan's operation; mucosal diseases without ulceration, e.g., Menetrier's disease, celiac disease, eosinophilic gastroenteritis; and immune diseases, e.g., systemic lupus erythematosus or food allergies, primarily to milk (see also Table 40-2 of Pediatric Gastrointestinal Disease Pathophysiology Diagnosis Management, Eds. Wyllie et al, Saunders Co. (1993), pages 536-543; which is incorporated by reference herein in its entirety). The antibodies can be administered to patients with cancer, autoimmune disease, vascular disease, bacterial infection, Celiac Disease, asthma, and irritable bowel synderome.

Anne

[annelb]

http://www.celiaccenter.org/
Dr. Fasano's home has a new look. There is lots to check out. Videos, news, research and a newsletter is coming. Worth the while to take a look. :cool:
Anne

[annelb]

Newest press release about Zonulin testing.
http://www.earthtimes.org/articles/show/news_press_release,71856.shtml

"We are pleased with the rapid enrollment of this study and look forward to reporting its results later this year," said Dr. Blake Paterson, CEO of Alba. "Previously reported AT-1001 clinical trial data has been promising and we expect that the results of our ongoing clinical evaluation will support our Phase IIb trial design." The 86 patients enrolled in the Phase IIa study were confirmed biopsy positive for CD and in compliance with a gluten-free diet for at least six months prior to enrollment. Patients were randomized into seven drug-treated and placebo groups and challenged three times a day with gluten for a 14 day period.

Anne

[NancyM]

I wonder how they can ethically give people on a placebo something that harms them?

[aklap]

It's all in the name of science (and informed consent).

http://clinicaltrials.gov/ct/info/resources;jsessionid=84BE905A6BB94BE08837A619EB48E F81

[annelb]

The difference here is that the doctors know gluten causes damage. Most trials don't include something that is known to cause illness. I don't think I would volunteer for this trial even if I had the "gold standard" diagnosis.

Even Dr. Fasano says this drug should be used only when there is a possibility of eating gluten. Zonulin is there for a reason. The immune system does not like to be fooled. I doubt it is a "cure" for CD.
Anne

[aklap]

The difference here is that the doctors know gluten causes damage.

I bet there's a whoooooole lot of other testing done with those same risks.

I would venture guess that there has to be human testing done in order to get it approved. In our case, we're for the most part happy doing the GF thing..so it's not as important to us. Lets look at other life saving drugs and see what risks were taken while testing them.

[annelb]

I bet there's a whoooooole lot of other testing done with those same risks.

I would venture guess that there has to be human testing done in order to get it approved. In our case, we're for the most part happy doing the GF thing..so it's not as important to us. Lets look at other life saving drugs and see what risks were taken while testing them.

Not sure. Usually it is one drug or treatment against another or against a placebo. I can't think of a trial where damage was caused on purpose.
Anne

[aklap]

Not sure. Usually it is one drug or treatment against another or against a placebo. I can't think of a trial where damage was caused on purpose.
Anne
Hmmm interesting research project :)

I have to believe, in all the drugs that have come about, there have been other trials where people were given something to cause a reaction or damage of some sort. How else are they going to know if the drug is doing what it is supposed to do?

[annelb]

Hmmm interesting research project :)

I have to believe, in all the drugs that have come about, there have been other trials where people were given something to cause a reaction or damage of some sort. How else are they going to know if the drug is doing what it is supposed to do?

The drugs are tested on people who already have the disease to see if the new medication helps or being tested on people who don't have a disease and they see how many get the disease with and without the drug that is being tested.

This is like putting people with asthma into a smoggy room to see if a drug works against a placebo. And they doing it over and over. Or maybe that has been done too??
Anne

[aklap]

This is like putting people with asthma into a smoggy room to see if a drug works against a placebo. And they doing it over and over. Or maybe that has been done too??
Anne
That's a great example!! How are they going to know the the asthma drug is working if they don't induce the problem?

Study of Oglemilast for the Treatment of Asthma (http://clinicaltrials.gov/ct/show/NCT00322686?order=16)

Further study details as provided by Forest Laboratories:

Primary Outcomes: To determine the effect of oglemilast in the prevention of bronchoconstriction after the administration of allergen, in comparison with placebo in patients with mild asthma

Secondary Outcomes: To evaluate the safety of oglemilast over 2 weeks as determined by adverse events,physical examinations, vital signs, electrocardiograms, and laboratory examinations
Expected Total Enrollment: 12


Ozone and Rhinovirus-Induced Disease in Asthmatics (http://clinicaltrials.gov/ct/show/NCT00013715?order=35)

In mild asthmatics, the study will investigate: (1) if exposure to ozone will enhance the viral infective process in the nasal epithelium, (2) the effect of ozone exposure on RV-induced inflammatory gene expression, mediator release and inflammatory cell influx into the upper and lower airways, and (3) the interactive effects of ozone and RV on airway reactivity. This information will improve our understanding of the risk associated with oxidant pollutant exposure in this population of individuals in whom RV infection may represent a significant health concern.

[annelb]

First, do no harm...unless it is in the name of scientific research.

Oh well, that statement was never part of the Hippocratic oath anyway. http://www.geocities.com/everwild7/noharm.html
Anne

[aklap]

Hehheeee I had looked that up yesterday and was going to post it if needed ;)

[annelb]

http://www.pr-inside.com/alba-therapeutics-corporation-reports-preliminary-r115861.htm

May 7 /PRNewswire/ -- Alba Therapeutics Corporation today announced preliminary results from its Phase IIa clinical trial for AT-1001 in subjects with Celiac Disease (CD), an autoimmune disease affecting over 3 million people in the United States. Alba's study, the first Phase IIa trial in CD and the first to assess dosing requirements for AT-1001 in CD, was designed to evaluate the safety, tolerability and efficacy of multiple doses of AT-1001 in CD subjects during a 2-week gluten challenge.

The randomized, double-blind, placebo-controlled clinical trial enrolled 86 patients who were confirmed biopsy positive for CD and in compliance with a gluten-free diet for at least six months prior to enrollment. Patients were randomized into seven drug-treated and placebo groups and challenged three times a day with gluten during a 14-day period. Four doses of the enteric coated oral formulation of AT-1001, all less than 10 mg, were given prior to each gluten challenge. Study endpoints included intestinal permeability (IP) -- a marker of disease state in CD -- as well as patient symptoms and outcomes, measured by two validated tests of gastrointestinal disease outcome: the Gastrointestinal Symptoms Rating Scale (GSRS) and the Psychological General Well-Being Index (PGWBI).

Preliminary analysis revealed the following:

-- At day 14, IP, as measured by the change in urinary lactulose-to-
mannitol (LA/MA) ratio, exhibited a dose dependent response. On day
21, one week after the final drug dosing and gluten challenge, the dose
dependent trend continued to statistically significant levels.

-- The GSRS and PGWBI provided additional efficacy signals that further
support the IP observations. Patients on the AT-1001 drug arms
performed better than those on the gluten/placebo arm. Analyses
demonstrated that several symptoms and outcomes improved at
statistically significant levels.

-- Safety and tolerability of multiple oral doses of AT-1001 in the
patient population was demonstrated. There were no Severe Adverse
Events and all Adverse Events were reported as mild or moderate.

"We are very encouraged by the preliminary data and look forward to applying the extensive knowledge gained in this Phase IIa exploratory clinical trial to a larger, highly powered Phase IIb gluten challenge study later this year" said Blake Paterson, M.D., Chief Executive Officer of Alba Therapeutics. Using the highly complex and ambitious seven arm study design for the Phase IIa trial, we repeated the proof of concept from the Phase Ib study, showed a statistically significant effect across a variety of measures and are well prepared to move the celiac program forward."

Based on these results, Alba will advance AT-1001 into a Phase IIb clinical study in CD subjects during the third quarter of 2007. The Phase IIb study, to be performed in multiple centers in the United States and Canada, will assess the efficacy of AT-1001 utilizing multiple endpoints, including a composite index of disease activity. The first patient is expected to be enrolled into this study in the third quarter of 2007, and the study should conclude in early 2008.


Anne

[JudyLV]

I am glad they are using a Psychological General Well-Being Index (PGWBI). I wonder how they rate this. I have a son who cries easily and becomes extremely angy if he gets even a trace amount of gluten. I feel badly for him when this happens because his poor behavior is not really his his fault but we all end up suffering. Sometimes when I see a child who has complete "lost it" and is in the midst of a tantrum I start thinking that some food might be the cause of the poor behavior.
--Judy