by wayne persky |
RSS Feed For decades, researchers have been searching for a "cure" for celiac disease, although their idea of a "cure" is a drug that a patient would have to take for the rest of their life, and in most cases, before every meal that contains gluten. By contrast, most patients consider a "cure" to be a complete resolution of symptoms, requiring no further treatments in the future.
Numerous drugs claimed to help with gluten digestion are available.
Over the years, researchers have developed several drugs that have been promoted as a treatment for celiac disease, (gluten sensitivity). While those drugs do help with the digestion of gluten, their efficacy is not perfect, so that their use may still allow the creation of enough partially digested peptides (amino acid chains) to provoke the immune system, so that some degree of inflammation and damage to the lining of the small intestine may continue to accrue, depending upon the magnitude of the gluten exposure, and the status of the individual patient's immune system (and probably, some degree of luck).
These products help when eating away from home.
For some patients using these products, the residual inflammation level resulting from a cross contaminated meal may be tolerable, while for others it may provoke a reaction (though certainly less serious than it would be without the use of the product). Typically, for most gluten sensitive individuals, the better products will prevent a reaction due to low level cross-contamination, but they're not capable of preventing a reaction to a major gluten exposure. For gluten sensitive individuals whose diet is regularly cross contaminated, their background inflammation level may be sufficient to cause their immune system sensitivity to remain somewhat elevated.
The next wave of treatments will be based on TG2 inhibitors.
Treatments based on the use of transglutaminase 2 (TG2) inhibitors have been suggested as a way to effectively prevent celiac disease, although much more research and clinical trials, remain to be done. TG2 inhibitors are compounds that inhibit the activity of the enzyme transglutaminase 2. TG2 is an enzyme that plays a role in various physiological processes, including cell signaling, apoptosis (programmed cell death), and the stabilization of the extracellular matrix. It's also involved in the pathogenesis of several diseases, including celiac disease. And although this has not yet been investigated by researchers, there's a good chance that it may be responsible for reactions caused by non-celiac gluten sensitivity.
In celiac disease, TG2 modifies gluten-derived peptides, making them more immunogenic (i.e., more likely to trigger an immune response). This process leads to an inflammatory response in the small intestine, causing damage to the intestinal lining and resulting in the symptoms of celiac disease.
In celiac disease, TG2 modifies gluten-derived peptides, making them more immunogenic (i.e., more likely to trigger an immune response). This process leads to an inflammatory response in the small intestine, causing damage to the intestinal lining and resulting in the symptoms of celiac disease.
TG2 inhibitors work by blocking the activity of TG2,
thereby reducing the modification of gluten peptides and potentially decreasing the immune response and intestinal damage in celiac disease patients. These inhibitors can potentially alleviate the symptoms of celiac disease and improve the quality of life for patients by targeting the underlying mechanism of the disease.
TG2 inhibitors come in different forms.
TG2 inhibitors can be classified into different types based on their chemical structure and mode of action. Some inhibitors are small molecules, while others are peptides or antibodies designed to specifically target TG2.
The development of TG2 inhibitors is an active area of research, with several potential compounds being studied for their efficacy and safety in treating celiac disease. Clinical trials are necessary to determine the therapeutic potential of these inhibitors and their role in the management of celiac disease.
By inhibiting TG2, these compounds may reduce the immune response to gluten, leading to fewer symptoms and less intestinal damage. TG2 inhibitors could provide an additional treatment option for celiac disease patients, complementing a gluten-free diet and potentially allowing for more dietary flexibility. As a targeted therapy, TG2 inhibitors offer a more specific approach to managing celiac disease compared to general immunosuppressive treatments.
The development of TG2 inhibitors is an active area of research, with several potential compounds being studied for their efficacy and safety in treating celiac disease. Clinical trials are necessary to determine the therapeutic potential of these inhibitors and their role in the management of celiac disease.
By inhibiting TG2, these compounds may reduce the immune response to gluten, leading to fewer symptoms and less intestinal damage. TG2 inhibitors could provide an additional treatment option for celiac disease patients, complementing a gluten-free diet and potentially allowing for more dietary flexibility. As a targeted therapy, TG2 inhibitors offer a more specific approach to managing celiac disease compared to general immunosuppressive treatments.
A recent Science Daily article describes ongoing research
regarding the possible use of TG2 inhibitors to treat celiac disease (Tampere Uniersity, 2024, June 24).1 Although the article seems to suggest that this concept is a new innovation, the research (searching for transglutaminase-based solutions) has actually been ongoing for roughly 5 decades.
Tissue transglutaminase was identified as the autoantigen of celiac disease in an article published in Nature Medicine back in 1997 (Dieterich, et al., 1997).2 And an article by Matthew Siegel and Chaitan Khosla published in Pharmacology & Therapeutics discusses the multifunctional enzyme transglutaminase 2 (TG2) and its role in various disease states, including celiac disease.3 The article provides a comprehensive overview of TG2 inhibitors and their potential therapeutic applications. Here are the key implications for treating gluten sensitivity and celiac disease based on this research:
The review highlights the identification of various small molecule and peptidomimetic inhibitors targeting the TG2 active site. These inhibitors can potentially block the enzymatic activity of TG2, preventing the modification of gluten peptides and the subsequent immune response: By inhibiting TG2, these compounds could reduce the immune system's reaction to gluten, thereby alleviating the symptoms of celiac disease. This could be particularly beneficial for patients who have difficulty maintaining a strict gluten-free diet.
TG2 inhibitors could allow for more dietary flexibility, reducing the burden of a gluten-free diet and improving the overall quality of life for celiac disease patients. TG2 is implicated in various other diseases, including neurodegenerative diseases and certain cancers. This suggests that TG2 inhibitors might have broader therapeutic applications beyond celiac disease, potentially offering new treatment avenues for these conditions (MC might be one of these conditions).
Tissue transglutaminase was identified as the autoantigen of celiac disease in an article published in Nature Medicine back in 1997 (Dieterich, et al., 1997).2 And an article by Matthew Siegel and Chaitan Khosla published in Pharmacology & Therapeutics discusses the multifunctional enzyme transglutaminase 2 (TG2) and its role in various disease states, including celiac disease.3 The article provides a comprehensive overview of TG2 inhibitors and their potential therapeutic applications. Here are the key implications for treating gluten sensitivity and celiac disease based on this research:
The review highlights the identification of various small molecule and peptidomimetic inhibitors targeting the TG2 active site. These inhibitors can potentially block the enzymatic activity of TG2, preventing the modification of gluten peptides and the subsequent immune response: By inhibiting TG2, these compounds could reduce the immune system's reaction to gluten, thereby alleviating the symptoms of celiac disease. This could be particularly beneficial for patients who have difficulty maintaining a strict gluten-free diet.
TG2 inhibitors could allow for more dietary flexibility, reducing the burden of a gluten-free diet and improving the overall quality of life for celiac disease patients. TG2 is implicated in various other diseases, including neurodegenerative diseases and certain cancers. This suggests that TG2 inhibitors might have broader therapeutic applications beyond celiac disease, potentially offering new treatment avenues for these conditions (MC might be one of these conditions).
Clinical trials are underway.
Ensuring that TG2 inhibitors are safe and effective for long-term use is a primary concern. The results of clinical trials will be crucial in addressing these issues. The effectiveness of TG2 inhibitors may vary among individuals, and personalized approaches may be needed to optimize treatment outcomes. While promising, TG2 inhibitors are likely to be used alongside a gluten-free diet rather than replacing it entirely. Researchers continue to search for a "cure"for celiac disease, but it seems that the best they are ever able to do is develop another “treatment". Hopefully this category of treatments will be more effective than the other treatments already on the market.
This class of treatments may be beneficial for many MC patients.
This approach appears to have the potential to be useful for many MC patients who have difficulty either achieving, or maintaining remission because of cross-contamination issues with their diet. It may turn out to be the missing link in the treatment of the most severe MC cases that refuse to be resolved despite dedicated efforts. And hopefully, unless something unforeseen develops, treatments in this category might be free of any undesirable side effects, although that remains to be seen.
References
1. Tampere Uniersity. (2024, June 24). New study demonstrates the efficacy of a promising celiac disease drug at the molecular level. ScienceDaily, Retrieved from https://www.sciencedaily.com/releases/2024/06/240624125521.htm
2. Dieterich, W,, Ehnis, T., Bauer, M., Donner, P., Volta, U., Riecken, E. O, and Schuppan, D. (1997). Identification of tissue transglutaminase as the autoantigen of celiac disease. Nature Medicine, Jul;3(7),pp 797-801. Retrieved from https://pubmed.ncbi.nlm.nih.gov/9212111/
3. Siegel, M., Khosla, C. (2007 ). Transglutaminase 2 inhibitors and their therapeutic role in disease states. Pharmacology & Therapeutics, 115(2), pp 232–245. Retrieved from https://pubmed.ncbi.nlm.nih.gov/17582505/
