The Celiac Disease Foundation In Brief
Volume 4
Q. How did the concept of ALV003 as a possible treatment for celiac disease come about?
A. Celiac disease is an autoimmune disorder, which in genetically susceptible individuals is triggered by the ingestion of gluten-containing foods. There are several potential points in the immune-inflammatory cascade where one could potentially intercede in an attempt to disrupt that process. The approach with ALV003 is elegant in its simplicity, and we hope to be able to show in clinical trials that it breaks down gluten before the gluten can cause inflammatory injury to the intestinal mucosa.
ALV003 is a mixture of two gluten-specific proteases, first identified by researchers at Stanford University by screening of naturally-occurring glutenases for the desired characteristics of stability in the stomach environment. These glutenases have been shown, in vitro, to target the glutamine and proline-rich peptide sequences in gluten that appear to drive the immunologic response in celiac disease patients. These proteins were then cloned and expressed and put into an E. coli expression system for scale-up production. We are developing ALV003 as an adjunct to the gluten-free diet (GFD), not a replacement.
Q. Why celiac disease?
A. Celiac disease has been increasing in prevalence worldwide over the past several decades. There are no pharmaceutical treatments available currently, and the only treatment option for patients is strict exclusion of dietary gluten which is almost impossible to achieve. The GFD is expensive and variably effective; only up to a third of patients who are on a GFD show complete healing of the small bowel mucosal membrane. The majority of patients continue to have episodic symptoms and evidence of mucosal inflammation despite attempts to adhere to the GFD.
We felt that there was a need for a non-dietary, pharmaceutical treatment for celiac disease that would work as an adjunct to the GFD.
Q. How are drugs developed for human use?
A. The drug approval process is both time-consuming and costly but,-in the end, when a drug is approved by the FDA or similar regulatory authorities in other countries, it has been shown to be both effective and safe in rigorously-conducted clinical trials. The first steps for development start with extensive characterization of the biology and mechanism of action of the compound. Then there are animal studies to evaluate the biologic effects and toxicology that must be completed prior to introduction into human clinical trials. The "phase 1" studies are the first-in-human studies, and are typically small in size, involving approximately 20-80 patients or healthy volunteers and are focused on safety of single, and then multiple doses of the drug. Phase 2 studies are the first studies designed to evaluate the potential effectiveness of the drug, as well as expanded safety assessments in larger numbers of patients. These studies typically enroll approximately 100-300 patients. Phase 3 studies are often referred to as "registrational" or "pivotal" trials and are the basis by which the regulatory authorities determine if the drug should be approved for commercialization. These trials often enroll approximately 1000 to 3000 patients. Lastly, there are phase 4 post-marketing studies that are used to assess long-term safety in the large number of patients who are being prescribed the drug. This long and arduous drug approval process should give patients the comfort of knowing that the drugs have been thoroughly evaluated for safety and efficacy by the time they are commercially available.
Q. How important is it to have celiac disease patients participate in clinical trials?
A. The companies that sponsor clinical trials are concerned with the health and safety of patient volunteers and ensure that the data derived from their participation can help to better understand the disease and its treatment. As you can tell by the numbers of patients needed to get a drug approved and available to patients who need them, it is crucial that patients be willing to participate in clinical trials.
Q. We read recently that Alvine reported positive phase 2 data for ALV003. Can you tell us what is next for ALV003 and where your clinical trials will be conducted?
A. Alvine presented data at an international gastroenterology meeting that took place in October 2011, where we showed in a rigorously-conducted, controlled clinical trial that ALV003, when administered in the context of "everyday-GFD" meals plus added gluten, was able to diminish gluten-induced mucosal injury. We are planning additional phase 2 clinical trials designed to assess the effects of ALV003, as an adjunct to a GFD, on symptoms as well as on mucosal inflammation and celiac antibody levels in celiac disease patients. We plan to conduct these studies in the United States and Canada. Depending on the outcome, we hope to then move on to phase 3 clinical trials in both North America and Europe.
Q. How did the concept of ALV003 as a possible treatment for celiac disease come about?
A. Celiac disease is an autoimmune disorder, which in genetically susceptible individuals is triggered by the ingestion of gluten-containing foods. There are several potential points in the immune-inflammatory cascade where one could potentially intercede in an attempt to disrupt that process. The approach with ALV003 is elegant in its simplicity, and we hope to be able to show in clinical trials that it breaks down gluten before the gluten can cause inflammatory injury to the intestinal mucosa.
ALV003 is a mixture of two gluten-specific proteases, first identified by researchers at Stanford University by screening of naturally-occurring glutenases for the desired characteristics of stability in the stomach environment. These glutenases have been shown, in vitro, to target the glutamine and proline-rich peptide sequences in gluten that appear to drive the immunologic response in celiac disease patients. These proteins were then cloned and expressed and put into an E. coli expression system for scale-up production. We are developing ALV003 as an adjunct to the gluten-free diet (GFD), not a replacement.
Q. Why celiac disease?
A. Celiac disease has been increasing in prevalence worldwide over the past several decades. There are no pharmaceutical treatments available currently, and the only treatment option for patients is strict exclusion of dietary gluten which is almost impossible to achieve. The GFD is expensive and variably effective; only up to a third of patients who are on a GFD show complete healing of the small bowel mucosal membrane. The majority of patients continue to have episodic symptoms and evidence of mucosal inflammation despite attempts to adhere to the GFD.
We felt that there was a need for a non-dietary, pharmaceutical treatment for celiac disease that would work as an adjunct to the GFD.
Q. How are drugs developed for human use?
A. The drug approval process is both time-consuming and costly but,-in the end, when a drug is approved by the FDA or similar regulatory authorities in other countries, it has been shown to be both effective and safe in rigorously-conducted clinical trials. The first steps for development start with extensive characterization of the biology and mechanism of action of the compound. Then there are animal studies to evaluate the biologic effects and toxicology that must be completed prior to introduction into human clinical trials. The "phase 1" studies are the first-in-human studies, and are typically small in size, involving approximately 20-80 patients or healthy volunteers and are focused on safety of single, and then multiple doses of the drug. Phase 2 studies are the first studies designed to evaluate the potential effectiveness of the drug, as well as expanded safety assessments in larger numbers of patients. These studies typically enroll approximately 100-300 patients. Phase 3 studies are often referred to as "registrational" or "pivotal" trials and are the basis by which the regulatory authorities determine if the drug should be approved for commercialization. These trials often enroll approximately 1000 to 3000 patients. Lastly, there are phase 4 post-marketing studies that are used to assess long-term safety in the large number of patients who are being prescribed the drug. This long and arduous drug approval process should give patients the comfort of knowing that the drugs have been thoroughly evaluated for safety and efficacy by the time they are commercially available.
Q. How important is it to have celiac disease patients participate in clinical trials?
A. The companies that sponsor clinical trials are concerned with the health and safety of patient volunteers and ensure that the data derived from their participation can help to better understand the disease and its treatment. As you can tell by the numbers of patients needed to get a drug approved and available to patients who need them, it is crucial that patients be willing to participate in clinical trials.
Q. We read recently that Alvine reported positive phase 2 data for ALV003. Can you tell us what is next for ALV003 and where your clinical trials will be conducted?
A. Alvine presented data at an international gastroenterology meeting that took place in October 2011, where we showed in a rigorously-conducted, controlled clinical trial that ALV003, when administered in the context of "everyday-GFD" meals plus added gluten, was able to diminish gluten-induced mucosal injury. We are planning additional phase 2 clinical trials designed to assess the effects of ALV003, as an adjunct to a GFD, on symptoms as well as on mucosal inflammation and celiac antibody levels in celiac disease patients. We plan to conduct these studies in the United States and Canada. Depending on the outcome, we hope to then move on to phase 3 clinical trials in both North America and Europe.
Developmental Therapies for Celiac Disease
Volume 4
Q. How did the concept of ALV003 as a possible treatment for celiac disease come about?
A. Celiac disease is an autoimmune disorder, which in genetically susceptible individuals is triggered by the ingestion of gluten-containing foods. There are several potential points in the immune-inflammatory cascade where one could potentially intercede in an attempt to disrupt that process. The approach with ALV003 is elegant in its simplicity, and we hope to be able to show in clinical trials that it breaks down gluten before the gluten can cause inflammatory injury to the intestinal mucosa.
ALV003 is a mixture of two gluten-specific proteases, first identified by researchers at Stanford University by screening of naturally-occurring glutenases for the desired characteristics of stability in the stomach environment. These glutenases have been shown, in vitro, to target the glutamine and proline-rich peptide sequences in gluten that appear to drive the immunologic response in celiac disease patients. These proteins were then cloned and expressed and put into an E. coli expression system for scale-up production. We are developing ALV003 as an adjunct to the gluten-free diet (GFD), not a replacement.
Q. Why celiac disease?
A. Celiac disease has been increasing in prevalence worldwide over the past several decades. There are no pharmaceutical treatments available currently, and the only treatment option for patients is strict exclusion of dietary gluten which is almost impossible to achieve. The GFD is expensive and variably effective; only up to a third of patients who are on a GFD show complete healing of the small bowel mucosal membrane. The majority of patients continue to have episodic symptoms and evidence of mucosal inflammation despite attempts to adhere to the GFD.
We felt that there was a need for a non-dietary, pharmaceutical treatment for celiac disease that would work as an adjunct to the GFD.
Q. How are drugs developed for human use?
A. The drug approval process is both time-consuming and costly but,-in the end, when a drug is approved by the FDA or similar regulatory authorities in other countries, it has been shown to be both effective and safe in rigorously-conducted clinical trials. The first steps for development start with extensive characterization of the biology and mechanism of action of the compound. Then there are animal studies to evaluate the biologic effects and toxicology that must be completed prior to introduction into human clinical trials. The "phase 1" studies are the first-in-human studies, and are typically small in size, involving approximately 20-80 patients or healthy volunteers and are focused on safety of single, and then multiple doses of the drug. Phase 2 studies are the first studies designed to evaluate the potential effectiveness of the drug, as well as expanded safety assessments in larger numbers of patients. These studies typically enroll approximately 100-300 patients. Phase 3 studies are often referred to as "registrational" or "pivotal" trials and are the basis by which the regulatory authorities determine if the drug should be approved for commercialization. These trials often enroll approximately 1000 to 3000 patients. Lastly, there are phase 4 post-marketing studies that are used to assess long-term safety in the large number of patients who are being prescribed the drug. This long and arduous drug approval process should give patients the comfort of knowing that the drugs have been thoroughly evaluated for safety and efficacy by the time they are commercially available.
Q. How important is it to have celiac disease patients participate in clinical trials?
A. The companies that sponsor clinical trials are concerned with the health and safety of patient volunteers and ensure that the data derived from their participation can help to better understand the disease and its treatment. As you can tell by the numbers of patients needed to get a drug approved and available to patients who need them, it is crucial that patients be willing to participate in clinical trials.
Q. We read recently that Alvine reported positive phase 2 data for ALV003. Can you tell us what is next for ALV003 and where your clinical trials will be conducted?
A. Alvine presented data at an international gastroenterology meeting that took place in October 2011, where we showed in a rigorously-conducted, controlled clinical trial that ALV003, when administered in the context of "everyday-GFD" meals plus added gluten, was able to diminish gluten-induced mucosal injury. We are planning additional phase 2 clinical trials designed to assess the effects of ALV003, as an adjunct to a GFD, on symptoms as well as on mucosal inflammation and celiac antibody levels in celiac disease patients. We plan to conduct these studies in the United States and Canada. Depending on the outcome, we hope to then move on to phase 3 clinical trials in both North America and Europe.
Q. How did the concept of ALV003 as a possible treatment for celiac disease come about?
A. Celiac disease is an autoimmune disorder, which in genetically susceptible individuals is triggered by the ingestion of gluten-containing foods. There are several potential points in the immune-inflammatory cascade where one could potentially intercede in an attempt to disrupt that process. The approach with ALV003 is elegant in its simplicity, and we hope to be able to show in clinical trials that it breaks down gluten before the gluten can cause inflammatory injury to the intestinal mucosa.
ALV003 is a mixture of two gluten-specific proteases, first identified by researchers at Stanford University by screening of naturally-occurring glutenases for the desired characteristics of stability in the stomach environment. These glutenases have been shown, in vitro, to target the glutamine and proline-rich peptide sequences in gluten that appear to drive the immunologic response in celiac disease patients. These proteins were then cloned and expressed and put into an E. coli expression system for scale-up production. We are developing ALV003 as an adjunct to the gluten-free diet (GFD), not a replacement.
Q. Why celiac disease?
A. Celiac disease has been increasing in prevalence worldwide over the past several decades. There are no pharmaceutical treatments available currently, and the only treatment option for patients is strict exclusion of dietary gluten which is almost impossible to achieve. The GFD is expensive and variably effective; only up to a third of patients who are on a GFD show complete healing of the small bowel mucosal membrane. The majority of patients continue to have episodic symptoms and evidence of mucosal inflammation despite attempts to adhere to the GFD.
We felt that there was a need for a non-dietary, pharmaceutical treatment for celiac disease that would work as an adjunct to the GFD.
Q. How are drugs developed for human use?
A. The drug approval process is both time-consuming and costly but,-in the end, when a drug is approved by the FDA or similar regulatory authorities in other countries, it has been shown to be both effective and safe in rigorously-conducted clinical trials. The first steps for development start with extensive characterization of the biology and mechanism of action of the compound. Then there are animal studies to evaluate the biologic effects and toxicology that must be completed prior to introduction into human clinical trials. The "phase 1" studies are the first-in-human studies, and are typically small in size, involving approximately 20-80 patients or healthy volunteers and are focused on safety of single, and then multiple doses of the drug. Phase 2 studies are the first studies designed to evaluate the potential effectiveness of the drug, as well as expanded safety assessments in larger numbers of patients. These studies typically enroll approximately 100-300 patients. Phase 3 studies are often referred to as "registrational" or "pivotal" trials and are the basis by which the regulatory authorities determine if the drug should be approved for commercialization. These trials often enroll approximately 1000 to 3000 patients. Lastly, there are phase 4 post-marketing studies that are used to assess long-term safety in the large number of patients who are being prescribed the drug. This long and arduous drug approval process should give patients the comfort of knowing that the drugs have been thoroughly evaluated for safety and efficacy by the time they are commercially available.
Q. How important is it to have celiac disease patients participate in clinical trials?
A. The companies that sponsor clinical trials are concerned with the health and safety of patient volunteers and ensure that the data derived from their participation can help to better understand the disease and its treatment. As you can tell by the numbers of patients needed to get a drug approved and available to patients who need them, it is crucial that patients be willing to participate in clinical trials.
Q. We read recently that Alvine reported positive phase 2 data for ALV003. Can you tell us what is next for ALV003 and where your clinical trials will be conducted?
A. Alvine presented data at an international gastroenterology meeting that took place in October 2011, where we showed in a rigorously-conducted, controlled clinical trial that ALV003, when administered in the context of "everyday-GFD" meals plus added gluten, was able to diminish gluten-induced mucosal injury. We are planning additional phase 2 clinical trials designed to assess the effects of ALV003, as an adjunct to a GFD, on symptoms as well as on mucosal inflammation and celiac antibody levels in celiac disease patients. We plan to conduct these studies in the United States and Canada. Depending on the outcome, we hope to then move on to phase 3 clinical trials in both North America and Europe.
Developmental Therapies for Celiac Disease
Receiving therapeutic treatments for Celiac Disease may one day be as simple as taking your daily vitamins. The following four treatments were possible treatments discussed at last years’ Celiac Disease Center at Columbia University Medical Center.
1) Enzyme and vaccine therapy. Enzyme therapy would involve introducing the necessary enzymes into the gut while vaccine therapy would instruct a person’s immune system to ignore gluten.
2) Routine intestinal biopsies. Biopsies would help patients monitor the healing status of small intestinal mucosa.
3) Immunosuppressants, steroids and enhanced nutritional support are needed for patients suffering from refractory CD where intestinal villi remain damaged despite a GF diet.
4) The dynamic gut bacteria micobiome may play a future role in managing CD. Provided from the mother at birth, present, absent or change to microbiome may relate to the onset of CD.
Celiac Disease is still finding its place in the everyday practice of American physicians. Finding treatments to manage symptoms or possibly cure Celiac Disease remains a new frontier for pharmaceutical companies, the FDA, and the patient.
The Role of Probiotics in Celiac Disease
The primary area of injury in celiac disease is the small bowel; however, there may be a relationship between what happens in the small bowel and the colon or large bowel. There are very large numbers of bacteria in the colon. Most of these are beneficial and when these thrive, they suppress the bad bacteria, which are present in the colon. What has been found is that celiac patients, in fact anyone on a gluten-free diet, have an altered make-up of bacteria in the colon which favors the unwanted bacteria.
Prebiotic Plant Fiber
A prebiotic is not a probiotic,-which are beneficial bacteria taken by mouth. Probiotics are present in yogurt, other dairy products and pills. Prebiotics, on the other hand, are the necessary plant fibers that contain both oligofructose and inulin. These two fibers are the main nourishment for the good bacteria that reside in the gut and are found in chicory root, Jerusalem artichoke, leeks, asparagus and others. There is now ample information in the medical literature to indicate that a prebiotic rich diet leads to demonstrable health benefits. Including:
§ Increased calcium absorption
§ Stronger bones and bone density
§ Enhanced immunity
§ Reduced allergies and asthma in infants and children
§ A lower blood triglyceride level
§ Appetite and weight control
§ Lower cancer factors in the gut
§ Other benefits, including an increased sense of well being
The Celiac Wheat-Prebiotic Dilemma
Nature has played a trick on celiac people. Wheat and wheat products provide over 80% of the prebiotics that North Americans ingest. Yet, celiac patients must carefully avoid wheat, barley and rye. How do they then feed their good colon bacteria and get the health benefits, as outlined above? They must favor the other vegetables and fruits, as listed in the prebiotic section below. Additionally, they should consider a gluten free prebiotic supplement such as Prebiotin.
Sources of Prebiotic Plant Fiber Oligofructose and Inulin:
§ Onion, garlic, leeks, Jerusalem artichokes, asparagus, chicory root, jicama, dandelion, banana, agave, and jams.
§ Whole, low fat, skim, dry, evaporated or condensed milk; buttermilk; cream; whipping cream; Velveeta cheese food; American cheese; all aged cheese such as Cheddar, Swiss, Edam and Parmesan
§ 100% meat (no grain additives); seafood; poultry (breaded with pure cornmeal, potato flour or rice flour); peanut butter; eggs; dried beans or peas and pork.
§ Cream of rice; cornmeal; hominy; rice; wild rice; gluten-free noodles; rice wafers; pure corn tortillas; specially prepared breads made with corn, rice, potato, soybean, tapioca, arrowroot, carob, buckwheat, millet, amaranth and quinoa flour
§ Plain, fresh, frozen, canned or dried fruit; all fruit juices, Fresh, frozen or canned vegetables; white and sweet potatoes; yams.
To read the story in its entirety: www.gicare.com/diets/gluten-free.aspx
Team Gluten-Free- Support the Cause.
Team Gluten-Free™ is a fund raising program that provides a simple way for runners, walkers, cyclists and triathletes to raise awareness and funds for Celiac Disease. The money raised by Team Gluten-Free™ participants goes directly towards summer camp scholarships for children on the gluten-free diet as well as Celiac Disease research, support and awareness programs. Team Gluten-Free™ is a fund raising arm of the Celiac Disease Foundation, a non-profit, public benefit corporation dedicated to the education of patients, families and health care professionals.
FAQ: All money raised will go directly to gluten-free summer camp scholarships for celiac children as well as celiac disease research and awareness programs. Choose any race in any city and complete the registration packet. Registration fees include your Team Gluten-Free™ shirt, training schedule and fundraising materials. Registration Cost: $25.00 for adults (18+), $15.00 for all others. Team members will be awarded prizes depending on the total money raised.
More information: http://www.teamglutenfree.org/media/pdf/Information_Packet2010.pdf
Effects of Untreated Celiac Disease.
According to the National Institute of Health (NIH) celiac disease is a multi-system disorder, and the clinical presentation is highly variable. Gastrointestinal manifestations may include diarrhea, weight loss, failure to grow, vomiting, abdominal pain, bloating and distension, anorexia, and constipation. The presence of obesity does not exclude the diagnosis.
Celiac Disease can play a role in all the following conditions: iron deficiency anemia, unexplained short stature, delayed puberty, infertility, recurrent fetal loss, osteoporosis, vitamin deficiencies, fatigue, protein calorie malnutrition, and dental enamel hypoplasia.
Celiac disease may also be associated with an autoimmune endocrinologic disorder such as thyroiditis and a variety of neuropsychiatric conditions such as depression, anxiety, peripheral neuropathy, ataxia, epilepsy with or without cerebral calcifications, and migraine headaches. Some studies report an increased risk of non-Hodgkin lymphoma in celiac disease, but often do not distinguish between the classic celiac associated lymphoma.Some researchers are convinced that gluten intolerance, whether or not it results in full-blown celiac disease, can impact mental functioning in some individuals and cause or aggravate Autism, Aspersers syndrome, Attention Deficit Disorder (ADD), and schizophrenia. The treatment of celiac disease remains a lifelong gluten-free diet, which results in remission for most individuals.
Is Fermented Wheat Flour Safe for People with Celiac Disease?
Is Fermented Wheat Flour Safe for People with Celiac Disease?
Science looks promising! The study, published in Clinical Gastroenterology and Hepatology, evaluated the safety of daily administration of baked goods made from a hydrolyzed form of wheat flour to patients with celiac disease – finding that fermented wheat flour with sourdough lactobacilli and fungal proteases decreases the concentration of gluten to safe levels.
“This is the first time that a wheat flour-derived product is shown to not be toxic after being given to celiac patients for 60 days,” said Dr Luigi Greco, of the University of Napes, Italy, lead author of the study.
Patients were randomly assigned to consumption of 200 grams per day of natural flour baked goods (NFBG) (containing 80127 ppm of gluten), extensively hydrolyzed flour baked goods (containing 2480 ppm residual gluten, or fully hydrolyzed baked goods (8 ppm residual gluten).
The five patients that ate the fully hydrolyzed baked goods reported no clinical complaints, and were found to have no changes in the levels of anti-tTG antibodies.
“In the future, cereals made through such biotechnology could also improve the nutritional and sensory properties of baked goods containing hydrolyzed gluten compared to products made of naturally gluten-free ingredients," added Greco.
Full story: http://mobile.foodnavigator-usa.com//Science-Nutrition/Fermented-wheat-flour-may-be-safe-for-celiac-patients-suggests-studyGluten Ease. What is it….Does it Work?
Gluten Ease is a dietary enzyme supplement and contains the four main digestive enzymes responsible to properly breakdown the food we ingest. Gluten Ease claims to help people with Celiac Disease or gluten-intolerance ingest small amounts of gluten while minimizing the uncomfortable side effects.
Enzyme 1: Amylase- responsible for the digestive breakdown of carbohydrates into simple sugars to provide the body with energy.
Enzyme 2: Cellulase- responsible for the breakdown of fiber found naturally in fruits and vegetables.
Enzyme 3: Lipase- responsible for the breakdown of fat from our foods. Lipase is produced by the pancreas and has been found to be low in people with pancreatitis and kidney disease. This enzyme has also been found helpful for people with Crohn’s, Cystic Fibrosis, and Celiac Disease. Enzyme 4: Protease- responsible for the breakdown of protein in the diet.
Verdict: the jury’s still out. While adding digestive enzymes to your daily diet has not been proven harmful; dietary supplements are not governed by the FDA. So the real question is: Are you getting what you’re paying for?
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