Promising New Research Results!

July 4, 2006

That being said, at least it might give my one yr old a chance to live a "normal" life. I dont care about myself, I would love for her to have a light at the end of the tunnel. I am very optimistic about this.

I'm not holding my breath for this - there will need to be at least 15+ years more research before this reaches the market. What works in the lab quite often doesn't work in living, breathing people.Maureen

July 4, 2006

That being said, at least it might give my one yr old a chance to live a "normal" life. I dont care about myself, I would love for her to have a light at the end of the tunnel. I am very optimistic about this.

I'm not holding my breath for this - there will need to be at least 15+ years more research before this reaches the market. What works in the lab quite often doesn't work in living, breathing people.Maureen

July 4, 2006

I'm so glad that research is being done. Each attempt, successful all the way to human consumption or not, increases awareness in the scientific community, stimulates new ideas for possible treatments and leads us closer to making celiac more manageable, more "mainstream" and hopefully better diagnosed.

Vicki

Orange, CA

July 4, 2006

I'm so glad that research is being done. Each attempt, successful all the way to human consumption or not, increases awareness in the scientific community, stimulates new ideas for possible treatments and leads us closer to making celiac more manageable, more "mainstream" and hopefully better diagnosed.

Vicki

Orange, CA

July 4, 2006

Public release date: 30-Jun-2006

http://www.eurekalert.org/pub_releases/2006-06/aps-csn062206.php

Contact: Mayer Resnick

mresnick@...

American Physiological Society

Celiac success: New enzyme efficiently degrades gluten in 'human

stomach' environment

End of the gluten-free diet in sight?

Bethesda, MD (June 30, 2006) - A new enzyme originally developed for

commercial food processing turns out to also quickly and

nearly-completely break down whole gluten molecules as well as the T

cell stimulatory peptides that cause celiac disease, a digestive

disease with no current effective treatment other than avoiding

wheat, barley or rye products.

In addition, the enzyme operates best in just the kind of

physiological environment found in the human stomach and works 60

times faster than an earlier promising enzyme, which was not

effective in acidic conditions and was inactivated by pepsin, both of

which are found in the stomach.

" On the basis of our results, there now is a realistic chance that

oral supplementation with an enzyme can ensure gluten degradation in

the stomach before reaching the small intestine, where it causes

problems for people with celiac disease, " according to Frits Koning,

researcher at the Leiden University Medical Center, The Netherlands,

who headed the team that has published a new research paper on its

work.

The paper, " Highly efficient gluten degradation with a newly

identified prolyl endoprotease: implications for celiac disease, " is

in the online American Journal of Physiology- Gastrointestinal and

Liver Physiology, published by The American Physiological Society.

Research was by Dariusz Stepniak, Liesbeth Spaenij-Dekking, Cristina

Mitea, e Moester, Arnoud de Ru, Baak-Pablo, van

Veelen and Frits Koning of Leiden University Medical Center, the

Netherlands, and Luppo Edens of DSM Food Specialties, Delft.

Clinical trials are likely next step

The new prolyl endoprotease (PEP) that was studied is derived from

Aspergillus niger (AN), a common fungus. Strains of A. niger are used

in industrial production of citric and gluconic acid as well as

producing several food grade enzymes.

Because there are no animal models of celiac disease, " the in vivo

efficacy of AN-PEP for gluten detoxification will ultimately have to

be addressed in clinical studies involving celiac patients. AN-PEP

appears to be a prime candidate for such clinical trials, " the paper

concluded. As for the timing of any such trials, Koning said: " This

is an option the team hopes to explore in the future. "

A disease of many paradoxes

Celiac disease affects about 2 million Americans and is also found in

Europe, India and parts of the Middle East. It's caused by an

uncontrolled immune response to wheat gluten and similar proteins of

rye and barley that cause diarrhea, malnutrition and failure to thrive

because it inhibits nutritional uptake.

" It's a Caucasian disease with a wide spectrum of symptoms; not all

patients are equally affected, but we do not understand why this is

the case, " Koning said. " It is known to be associated with the HLA-DQ2

gene, " he noted, " but while about 25% of the white population has this

gene, only about one in 100 get the disease, so it's really a quite

puzzling disease in many ways. "

Currently the only way to elude the disease symptoms is by avoiding

wheat, barley and rye products. " It sounds easy, but gluten especially

is widespread in Western diets, " Koning said. Gluten is often used as

a food additive because it adds protein content inexpensively and also

gives dough its elasticity and stickiness, which helps in

manufacturing.

For instance, Koning said: " Celiac patients can eat potato chips, but

not if they have added paprika or other spices because

they're 'glued' to the chip with gluten. "

AN-PEP outstrips earlier enzyme by 60-fold

Earlier attempts at finding non-human proteases for gluten

detoxification (first proposed in the late 1950s) focused on prolyl

oligopeptidases (POP), most notably FM-POP, which was able to break

down gluten sequences in vitro. However FM-POP's optimal operating pH

is between 7 and 8, so it didn't work well in the more acidic stomach

pH that goes down to 2 at one stage. A combination of pH 2 and pepsin

" immediately inactivated FM-POP, " the paper said. AN-PEP, on the other

hand, is active from pH 2-8, with optimum effect around pH 4. The

combination of pH 2 and pepsin didn't affect AN-PEP activity.

" An effective enzymatic treatment for celiac diseases requires means

of destroying all or at least the vast majority of gluten derived T

cell stimulatory sequences, " the paper said. The key to this is to

break the large gluten molecules (large peptides and intact proteins)

into smaller pieces before they leave the stomach. Because food stays

in the stomach one to four hours, speed of protein degradation is

also important. Mass spectrometry comparisons showed

that " degradation of gluten peptides by AN-PEP was on average [about

4 minutes, or] 60 times faster than degradation by FM-POP, " the paper

reported.

In addition to its ability to perform as a potential oral enzymatic

therapy because it " is capable of degrading intact gluten molecules

and T cell stimulatory epitopes from gluten into harmless fragments "

AN-PEP has several additional commercial advantages, the paper

said: " The enzyme is extremely stable and can be produced at

acceptable cost at food grade quality in an industry setting. "

Celiac disease is an HLA-linked disease related to Type 1 diabetes and

rheumatoid arthritis in which autoimmune reactions cause the disease;

similarly, immune reactions can lead to organ transplant rejection.

Koning said it " isn't likely that AN-PEP would be of any therapeutic

value in any of these HLA-associated diseases " because Type 1 diabetes

and rheumatoid arthritis are real autoimmune diseases, where the

immune system attacks parts of the body. In celiac disease, it is the

gluten that is the target, not the body.

Reminder warning on early introduction of gluten products

Koning said feeding wheat (or barley or rye) products to infants

before they're 6 months old isn't recommended because once an immune

response develops " immuno-memory builds up and it doesn't go away. "

Indeed, Koning noted that in Sweden some years ago gluten was

introduced into baby food, which led to a five-fold increase in

celiac disease. The problem disappeared when gluten was removed.

###

Source and funding/support

The paper, " Highly efficient gluten degradation with a newly

identified prolyl endoprotease: implications for celiac disease, " is

in the online American Journal of Physiology-Gastrointestinal and

Liver Physiology, published by The American Physiological Society.

Research was by Dariusz Stepniak, Liesbeth Spaenij-Dekking, Cristina

Mitea, e Moester, Arnoud de Ru, Baak-Pablo, van

Veelen and Frits Koning, Department of Immunohematology and Blood

Transfusion, Leiden University Medical Center, Leiden, the

Netherlands, and Luppo Edens of DSM Food Specialties, Delft, a

subsidiary of Koninklijke DSM N.V., a Dutch chemical conglomerate.

July 4, 2006

I'm not holding my breath for this - there will need to be at least

15+ years more research before this reaches the market. What works

in the lab quite often doesn't work in living, breathing people.

Maureen

>

> Public release date: 30-Jun-2006

> http://www.eurekalert.org/pub_releases/2006-06/aps-csn062206.php

>

> Contact: Mayer Resnick

> mresnick@...

>

> American Physiological Society

>

> Celiac success: New enzyme efficiently degrades gluten in 'human

> stomach' environment

>

> End of the gluten-free diet in sight?

>

> Bethesda, MD (June 30, 2006) - A new enzyme originally developed

for

> commercial food processing turns out to also quickly and

> nearly-completely break down whole gluten molecules as well as the

T

> cell stimulatory peptides that cause celiac disease, a digestive

> disease with no current effective treatment other than avoiding

> wheat, barley or rye products.

>

> In addition, the enzyme operates best in just the kind of

> physiological environment found in the human stomach and works 60

> times faster than an earlier promising enzyme, which was not

> effective in acidic conditions and was inactivated by pepsin, both

of

> which are found in the stomach.

>

> " On the basis of our results, there now is a realistic chance that

> oral supplementation with an enzyme can ensure gluten degradation

in

> the stomach before reaching the small intestine, where it causes

> problems for people with celiac disease, " according to Frits

Koning,

> researcher at the Leiden University Medical Center, The

Netherlands,

> who headed the team that has published a new research paper on its

> work.

>

> The paper, " Highly efficient gluten degradation with a newly

> identified prolyl endoprotease: implications for celiac disease, "

is

> in the online American Journal of Physiology- Gastrointestinal and

> Liver Physiology, published by The American Physiological Society.

> Research was by Dariusz Stepniak, Liesbeth Spaenij-Dekking,

Cristina

> Mitea, e Moester, Arnoud de Ru, Baak-Pablo, van

> Veelen and Frits Koning of Leiden University Medical Center, the

> Netherlands, and Luppo Edens of DSM Food Specialties, Delft.

>

> Clinical trials are likely next step

>

> The new prolyl endoprotease (PEP) that was studied is derived from

> Aspergillus niger (AN), a common fungus. Strains of A. niger are

used

> in industrial production of citric and gluconic acid as well as

> producing several food grade enzymes.

>

> Because there are no animal models of celiac disease, " the in vivo

> efficacy of AN-PEP for gluten detoxification will ultimately have

to

> be addressed in clinical studies involving celiac patients. AN-PEP

> appears to be a prime candidate for such clinical trials, " the

paper

> concluded. As for the timing of any such trials, Koning

said: " This

> is an option the team hopes to explore in the future. "

>

> A disease of many paradoxes

>

> Celiac disease affects about 2 million Americans and is also found

in

> Europe, India and parts of the Middle East. It's caused by an

> uncontrolled immune response to wheat gluten and similar proteins

of

> rye and barley that cause diarrhea, malnutrition and failure to

thrive

> because it inhibits nutritional uptake.

>

> " It's a Caucasian disease with a wide spectrum of symptoms; not all

> patients are equally affected, but we do not understand why this

is

> the case, " Koning said. " It is known to be associated with the HLA-

DQ2

> gene, " he noted, " but while about 25% of the white population has

this

> gene, only about one in 100 get the disease, so it's really a quite

> puzzling disease in many ways. "

>

> Currently the only way to elude the disease symptoms is by avoiding

> wheat, barley and rye products. " It sounds easy, but gluten

especially

> is widespread in Western diets, " Koning said. Gluten is often used

as

> a food additive because it adds protein content inexpensively and

also

> gives dough its elasticity and stickiness, which helps in

> manufacturing.

>

> For instance, Koning said: " Celiac patients can eat potato chips,

but

> not if they have added paprika or other spices because

> they're 'glued' to the chip with gluten. "

>

> AN-PEP outstrips earlier enzyme by 60-fold

>

> Earlier attempts at finding non-human proteases for gluten

> detoxification (first proposed in the late 1950s) focused on prolyl

> oligopeptidases (POP), most notably FM-POP, which was able to

break

> down gluten sequences in vitro. However FM-POP's optimal operating

pH

> is between 7 and 8, so it didn't work well in the more acidic

stomach

> pH that goes down to 2 at one stage. A combination of pH 2 and

pepsin

> " immediately inactivated FM-POP, " the paper said. AN-PEP, on the

other

> hand, is active from pH 2-8, with optimum effect around pH 4. The

> combination of pH 2 and pepsin didn't affect AN-PEP activity.

>

> " An effective enzymatic treatment for celiac diseases requires

means

> of destroying all or at least the vast majority of gluten derived

T

> cell stimulatory sequences, " the paper said. The key to this is to

> break the large gluten molecules (large peptides and intact

proteins)

> into smaller pieces before they leave the stomach. Because food

stays

> in the stomach one to four hours, speed of protein degradation is

> also important. Mass spectrometry comparisons showed

> that " degradation of gluten peptides by AN-PEP was on average

[about

> 4 minutes, or] 60 times faster than degradation by FM-POP, " the

paper

> reported.

>

> In addition to its ability to perform as a potential oral enzymatic

> therapy because it " is capable of degrading intact gluten

molecules

> and T cell stimulatory epitopes from gluten into harmless

fragments "

> AN-PEP has several additional commercial advantages, the paper

> said: " The enzyme is extremely stable and can be produced at

> acceptable cost at food grade quality in an industry setting. "

>

> Celiac disease is an HLA-linked disease related to Type 1 diabetes

and

> rheumatoid arthritis in which autoimmune reactions cause the

disease;

> similarly, immune reactions can lead to organ transplant

rejection.

> Koning said it " isn't likely that AN-PEP would be of any

therapeutic

> value in any of these HLA-associated diseases " because Type 1

diabetes

> and rheumatoid arthritis are real autoimmune diseases, where the

> immune system attacks parts of the body. In celiac disease, it is

the

> gluten that is the target, not the body.

>

> Reminder warning on early introduction of gluten products

>

> Koning said feeding wheat (or barley or rye) products to infants

> before they're 6 months old isn't recommended because once an

immune

> response develops " immuno-memory builds up and it doesn't go

away. "

> Indeed, Koning noted that in Sweden some years ago gluten was

> introduced into baby food, which led to a five-fold increase in

> celiac disease. The problem disappeared when gluten was removed.

> ###

> Source and funding/support

>

> The paper, " Highly efficient gluten degradation with a newly

> identified prolyl endoprotease: implications for celiac disease, "

is

> in the online American Journal of Physiology-Gastrointestinal and

> Liver Physiology, published by The American Physiological Society.

> Research was by Dariusz Stepniak, Liesbeth Spaenij-Dekking,

Cristina

> Mitea, e Moester, Arnoud de Ru, Baak-Pablo, van

> Veelen and Frits Koning, Department of Immunohematology and Blood

> Transfusion, Leiden University Medical Center, Leiden, the

> Netherlands, and Luppo Edens of DSM Food Specialties, Delft, a

> subsidiary of Koninklijke DSM N.V., a Dutch chemical conglomerate.

>

July 4, 2006

I'm not holding my breath for this - there will need to be at least

15+ years more research before this reaches the market. What works

in the lab quite often doesn't work in living, breathing people.

Maureen

>

> Public release date: 30-Jun-2006

> http://www.eurekalert.org/pub_releases/2006-06/aps-csn062206.php

>

> Contact: Mayer Resnick

> mresnick@...

>

> American Physiological Society

>

> Celiac success: New enzyme efficiently degrades gluten in 'human

> stomach' environment

>

> End of the gluten-free diet in sight?

>

> Bethesda, MD (June 30, 2006) - A new enzyme originally developed

for

> commercial food processing turns out to also quickly and

> nearly-completely break down whole gluten molecules as well as the

T

> cell stimulatory peptides that cause celiac disease, a digestive

> disease with no current effective treatment other than avoiding

> wheat, barley or rye products.

>

> In addition, the enzyme operates best in just the kind of

> physiological environment found in the human stomach and works 60

> times faster than an earlier promising enzyme, which was not

> effective in acidic conditions and was inactivated by pepsin, both

of

> which are found in the stomach.

>

> " On the basis of our results, there now is a realistic chance that

> oral supplementation with an enzyme can ensure gluten degradation

in

> the stomach before reaching the small intestine, where it causes

> problems for people with celiac disease, " according to Frits

Koning,

> researcher at the Leiden University Medical Center, The

Netherlands,

> who headed the team that has published a new research paper on its

> work.

>

> The paper, " Highly efficient gluten degradation with a newly

> identified prolyl endoprotease: implications for celiac disease, "

is

> in the online American Journal of Physiology- Gastrointestinal and

> Liver Physiology, published by The American Physiological Society.

> Research was by Dariusz Stepniak, Liesbeth Spaenij-Dekking,

Cristina

> Mitea, e Moester, Arnoud de Ru, Baak-Pablo, van

> Veelen and Frits Koning of Leiden University Medical Center, the

> Netherlands, and Luppo Edens of DSM Food Specialties, Delft.

>

> Clinical trials are likely next step

>

> The new prolyl endoprotease (PEP) that was studied is derived from

> Aspergillus niger (AN), a common fungus. Strains of A. niger are

used

> in industrial production of citric and gluconic acid as well as

> producing several food grade enzymes.

>

> Because there are no animal models of celiac disease, " the in vivo

> efficacy of AN-PEP for gluten detoxification will ultimately have

to

> be addressed in clinical studies involving celiac patients. AN-PEP

> appears to be a prime candidate for such clinical trials, " the

paper

> concluded. As for the timing of any such trials, Koning

said: " This

> is an option the team hopes to explore in the future. "

>

> A disease of many paradoxes

>

> Celiac disease affects about 2 million Americans and is also found

in

> Europe, India and parts of the Middle East. It's caused by an

> uncontrolled immune response to wheat gluten and similar proteins

of

> rye and barley that cause diarrhea, malnutrition and failure to

thrive

> because it inhibits nutritional uptake.

>

> " It's a Caucasian disease with a wide spectrum of symptoms; not all

> patients are equally affected, but we do not understand why this

is

> the case, " Koning said. " It is known to be associated with the HLA-

DQ2

> gene, " he noted, " but while about 25% of the white population has

this

> gene, only about one in 100 get the disease, so it's really a quite

> puzzling disease in many ways. "

>

> Currently the only way to elude the disease symptoms is by avoiding

> wheat, barley and rye products. " It sounds easy, but gluten

especially

> is widespread in Western diets, " Koning said. Gluten is often used

as

> a food additive because it adds protein content inexpensively and

also

> gives dough its elasticity and stickiness, which helps in

> manufacturing.

>

> For instance, Koning said: " Celiac patients can eat potato chips,

but

> not if they have added paprika or other spices because

> they're 'glued' to the chip with gluten. "

>

> AN-PEP outstrips earlier enzyme by 60-fold

>

> Earlier attempts at finding non-human proteases for gluten

> detoxification (first proposed in the late 1950s) focused on prolyl

> oligopeptidases (POP), most notably FM-POP, which was able to

break

> down gluten sequences in vitro. However FM-POP's optimal operating

pH

> is between 7 and 8, so it didn't work well in the more acidic

stomach

> pH that goes down to 2 at one stage. A combination of pH 2 and

pepsin

> " immediately inactivated FM-POP, " the paper said. AN-PEP, on the

other

> hand, is active from pH 2-8, with optimum effect around pH 4. The

> combination of pH 2 and pepsin didn't affect AN-PEP activity.

>

> " An effective enzymatic treatment for celiac diseases requires

means

> of destroying all or at least the vast majority of gluten derived

T

> cell stimulatory sequences, " the paper said. The key to this is to

> break the large gluten molecules (large peptides and intact

proteins)

> into smaller pieces before they leave the stomach. Because food

stays

> in the stomach one to four hours, speed of protein degradation is

> also important. Mass spectrometry comparisons showed

> that " degradation of gluten peptides by AN-PEP was on average

[about

> 4 minutes, or] 60 times faster than degradation by FM-POP, " the

paper

> reported.

>

> In addition to its ability to perform as a potential oral enzymatic

> therapy because it " is capable of degrading intact gluten

molecules

> and T cell stimulatory epitopes from gluten into harmless

fragments "

> AN-PEP has several additional commercial advantages, the paper

> said: " The enzyme is extremely stable and can be produced at

> acceptable cost at food grade quality in an industry setting. "

>

> Celiac disease is an HLA-linked disease related to Type 1 diabetes

and

> rheumatoid arthritis in which autoimmune reactions cause the

disease;

> similarly, immune reactions can lead to organ transplant

rejection.

> Koning said it " isn't likely that AN-PEP would be of any

therapeutic

> value in any of these HLA-associated diseases " because Type 1

diabetes

> and rheumatoid arthritis are real autoimmune diseases, where the

> immune system attacks parts of the body. In celiac disease, it is

the

> gluten that is the target, not the body.

>

> Reminder warning on early introduction of gluten products

>

> Koning said feeding wheat (or barley or rye) products to infants

> before they're 6 months old isn't recommended because once an

immune

> response develops " immuno-memory builds up and it doesn't go

away. "

> Indeed, Koning noted that in Sweden some years ago gluten was

> introduced into baby food, which led to a five-fold increase in

> celiac disease. The problem disappeared when gluten was removed.

> ###

> Source and funding/support

>

> The paper, " Highly efficient gluten degradation with a newly

> identified prolyl endoprotease: implications for celiac disease, "

is

> in the online American Journal of Physiology-Gastrointestinal and

> Liver Physiology, published by The American Physiological Society.

> Research was by Dariusz Stepniak, Liesbeth Spaenij-Dekking,

Cristina

> Mitea, e Moester, Arnoud de Ru, Baak-Pablo, van

> Veelen and Frits Koning, Department of Immunohematology and Blood

> Transfusion, Leiden University Medical Center, Leiden, the

> Netherlands, and Luppo Edens of DSM Food Specialties, Delft, a

> subsidiary of Koninklijke DSM N.V., a Dutch chemical conglomerate.

>

July 4, 2006

I have traveled worldwide repeatedly since diagnosis and eat out at least 5x a week. It doesnt slow *me* down - I just dont want my daughter to worry about it if she doesnt have to. It will be SO much easier on her and she wont feel left out of school parties, et al. Im sure any parent on here would prefer that for their child. Thats what I mean by "normal".

We already lead "normal" lives, and have always done so. Celiac is as big as you let it be: we travel (extensively), eat out, eat with friends, my son is on a sports team, goes to day camp, goes to art workshops, etc. We just do more prep work than other people.

July 4, 2006

I have traveled worldwide repeatedly since diagnosis and eat out at least 5x a week. It doesnt slow *me* down - I just dont want my daughter to worry about it if she doesnt have to. It will be SO much easier on her and she wont feel left out of school parties, et al. Im sure any parent on here would prefer that for their child. Thats what I mean by "normal".

We already lead "normal" lives, and have always done so. Celiac is as big as you let it be: we travel (extensively), eat out, eat with friends, my son is on a sports team, goes to day camp, goes to art workshops, etc. We just do more prep work than other people.

July 4, 2006

We already lead " normal " lives, and have always done so. Celiac is

as big as you let it be: we travel (extensively), eat out, eat with

friends, my son is on a sports team, goes to day camp, goes to art

workshops, etc. We just do more prep work than other people.

Breaking down gluten, which is the claim for this new enzyme, is

only one very small piece of treating celiac disease. They also need

to prove that the gluten byproducts are safe, and that the enzyme

itself is safe. For example, I am highly allergic to aspergillus (as

are many people) how would people who react to aspergillus react to

the isolated enzyme? What would the side effects of taking the

enzyme be? And there is a 100% chance there will be side effects -

the question is how big or how bad they will be.

And how will they test this? If you are familiar with human subject

protocols it becomes immediately apparent the ethics of such tests

are very difficult. Normally to prove effectiveness a blind study

would be done where subjects do not know if they receive the study

drug or a placebo; to test this subjects would have to both take the

drug and eat gluten. In a situation where it is known that subjects

getting the placebo will be harmed by eating gluten how do

researchers ethically test?

Also, molds, such as aspergillus are notorious for causing adverse

effects in humans. Much of the mania associated with the Salem witch

trials was believed to caused by grain contaminated with a mold.

Maybe this drug *many years from now* will help some celiacs. But we

will continue to lead our normal lives until then.

Maureen

>

> That being said, at least it might give my one yr old a chance to

live a

> " normal " life. I dont care about myself, I would love for her to

have a light

> at the end of the tunnel. I am very optimistic about this.

>

> In a message dated 7/4/2006 12:02:54 PM Eastern Standard Time,

> marcianar@... writes:

> I'm not holding my breath for this - there will need to be at

least

> 15+ years more research before this reaches the market. What

works

> in the lab quite often doesn't work in living, breathing people.

>

> Maureen

>

July 4, 2006