Patients with celiac disease may one day have a treatment that will help them digest hidden gluten in foods or allow them to enjoy a somewhat less restrictive diet.
Between 0.5% and 1% of individuals in the United States and Europe are believed to have celiac disease, and their inability to digest gluten protein in wheat and other grains may lead to serious gastrointestinal tract complications (van Heel DA and West J. Gut. 2006;55:1037-1046). Complications of celiac disease may include malnutrition, anemia, cancer, osteoporosis, and poor pregnancy outcomes.
Currently, the only treatment for patients with celiac disease is complete exclusion of foods such as breads, pastas, and many processed foods that contain gluten. Doing so is difficult, however, because gluten is ubiquitous and may not be listed as an ingredient in many food products. But recent research suggests that oral formulations of enzymes that are able to break down gluten may be a useful adjunct treatment to dietary restriction or may allow a somewhat less restrictive diet for patients with the disease.
In a trio of articles published in June, Chaitan Khosla, PhD, at Stanford University in Palo Alto, Calif, and colleagues presented evidence that suggests that a cocktail of enzymes might be a useful therapy for celiac disease. The scientists targeted components of gluten, structures consisting of proline and glutamine, that gut enzymes are unable to break down. Previously, scientists had identified bacterial prolyl endopeptidases (PEPs) as enzymes that might be useful in reducing the toxic effects of gluten because they cleave proline structures and can function in the duodenum.
Khosla and colleagues identified a second enzyme EP-B2, a glutamine-specific cysteine protease found in barley that is active under gastric conditions and could complement the activity of a PEP by cleaving glutamine (Bethune MT et al. Chem Biol. 2006;13:637-647). They demonstrated that the combination of EP-B2 and a PEP in concert with gut enzymes could break down the problematic components of gluten under conditions mimicking those of the gastrointestinal tract (Siegel M et al. Chem Biol. 2006;13:649-658). Finally, they demonstrated the ability of EP-B2 to help break down gluten in the rat gut (Gass et al. J Pharmacol Exp Ther. doi:10.1124/jpet.106.104 [published online ahead of print June 6, 2006]). The group had previously shown that PEP could help break down gluten in the rat gut (Piper JL et al. J Pharmacol Exp Ther. 2004;311:213-219).
“By adding glutamine- or proline-specific enzymes to the existing protease armamentarium [of the gut] you could make gluten as easy to digest as milk or meat,” Kola said.
Khosla said the next step will be launching clinical trials of EP-B2 in humans to understand how it would function in the human gastrointestinal tract, whether it would be safe, and how much it might help patients with celiac disease.
Currently, the physician's role in managing celiac disease often ends when they provide a diagnosis and refer the patient to a dietician, Khosla explained. However, an oral therapy that would be used in combination with dietary restriction could give physicians a tool to help improve outcomes for patients, he said.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
Instructions
Comments are moderated and will appear on the site at the discretion of the Journal of American Medical Association editors. Comments should not exceed 500 words of text and 10 references.
Do not submit personal medical questions or information that could identify a specific patient, questions about a particular case, or general inquiries to an author. Only content that has not been published, posted, or submitted elsewhere should be submitted. By submitting this Comment, you and any coauthors transfer copyright to the journal if your Comment is posted.
* = Required Field
Disclosure of Any Conflicts of Interest* Indicate all relevant conflicts of interest of each author below, including all relevant financial interests, activities, and relationships within the past 3 years including, but not limited to, employment, affiliation, grants or funding, consultancies, honoraria or payment, speakers’ bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. If all authors have none, check "No potential conflicts or relevant financial interests" in the box below. Please also indicate any funding received in support of this work. The information will be posted with your response.
Register and get free email Table of Contents alerts, saved searches, PowerPoint downloads, CME quizzes, and more
Subscribe for full-text access to content from 1998 forward and a host of useful features
Activate your current subscription (AMA members and current subscribers)
Some tools below are only available to our subscribers or users with an online account.
Download citation file:
Customize your page view by dragging & repositioning the boxes below.
and access these and other features:
Register Now
Enter your username and email address. We'll send you a reminder to the email address on record.
Athens and Shibboleth are access management services that provide single sign-on to protected resources. They replace the multiple user names and passwords necessary to access subscription-based content with a single user name and password that can be entered once per session. It operates independently of a user's location or IP address. If your institution uses Athens or Shibboleth authentication, please contact your site administrator to receive your user name and password.