Enzymatic detoxification of gluten by germinating wheat proteases: Implications for new treatment of celiac disease

Stenman, Satumarja; Venäläinen, Jarkko I.; Lindfors, Katri; Auriola, Seppo; Mauriala, Timo; Kaukovirta-Norja, Anu; Jantunen, Anna; Laurila, Kaija; Qiao, Shuo‐Wang; Sollid, Ludvig M.; Männistö, Pekka T.; Kaukinen, Katri; Mäki, Markku

doi:10.1080/07853890902878138

Cited by 50 publications

(47 citation statements)

References 40 publications

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“…While still not safe for Celiac patients [205], there are fewer immunoreactive peptides in sprouted products [202]. As for fermentation, lactic acid bacteria degrade some of the gliadins but multiple microbes appear to be needed to effectively degrade the majority of gliadin [206].…”

Section: Eat As If You Could Save the Planet And Win!mentioning

confidence: 99%

“Eat as If You Could Save the Planet and Win!” Sustainability Integration into Nutrition for Exercise and Sport

Meyer

Reguant-Closa

2017

Nutrients

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Today’s industrial food production contributes significantly to environmental degradation. Meat production accounts for the largest impact, including greenhouse gas emissions, land and water use. While food production and consumption are important aspects when addressing climate change, this article focuses predominantly on dietary change that promotes both health for planet and people with focus on athletes. Healthy, sustainable eating recommendations begin to appear in various governmental guidelines. However, there remains resistance to the suggested reductions in meat consumption. While food citizens are likely to choose what is good for them and the planet, others may not, unless healthy eating initiatives integrate creative food literacy approaches with experiential learning as a potential vehicle for change. This concept paper is organized in three sections: (1) Environmental impact of food; (2) health and sustainability connections; and (3) application in sports and exercise. For active individuals, this article focuses on the quantity of protein, highlighting meat and dairy, and quality of food, with topics such as organic production and biodiversity. Finally, the timing of when to integrate sustainability principles in sport nutrition is discussed, followed by practical applications for education and inclusion in team, institutional, and event operations.

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Section: Eat As If You Could Save the Planet And Win!mentioning

confidence: 99%

“Eat as If You Could Save the Planet and Win!” Sustainability Integration into Nutrition for Exercise and Sport

Meyer

Reguant-Closa

2017

Nutrients

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“…These enzymes are also able to exert their proteolytic function in the pH range present in the gastrointestinal tract, and they are at least moderately resistant to the prevailing harsh environment [20]. As shown in table 1, detoxification capacity of these enzymes has been supported by extensive in vitro, in vivo (in rats and macaques) and ex vivo (using biopsy-derived T cells and small bowel biopsies in organ culture systems) studies [21,22,23,24,25,26,27,28]. As PEP and EP-B2 are complementary as regards their sequence specificities, investigators have thought that a combination of these enzymes would be a dramatically superior therapeutic approach for the treatment of celiac disease [19].…”

Section: Rationale Behind Enzyme Supplementation Therapymentioning

confidence: 99%

“…Based on this, a combination enzyme product ALV003, consisting of 1:1 mixture of barley EP-B2 and Sphingomonas capsulata PEP has been formulated [23]. Following the line of thinking of the combination enzyme therapy, also an entire range of germinating cereal enzymes have been tested for their capability to degrade gluten [26,27]. The major advance in such an approach is that the protease preparation contains all the enzymes that are evolutionarily selected for total cleavage of storage proteins in germinating kernels.…”

Section: Rationale Behind Enzyme Supplementation Therapymentioning

confidence: 99%

Novel Treatments for Celiac Disease: Glutenases and Beyond

Kaukinen

Lindfors

2015

Dig Dis

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Currently, the only effective treatment for celiac disease is a strict lifelong gluten-free diet. However, gluten-free dieting is restrictive, difficult to maintain and nutritionally less than optimal. The improved knowledge on celiac disease pathogenesis has enabled researchers to suggest alternative strategies to treat the disorder. The drug development poses a challenge as any novel drug for celiac disease should be simultaneously effective and as safe as the gluten-free diet. The rationale behind enzyme supplementation therapy as a future treatment option for celiac patients lies in the fact that gluten is only poorly digested by gastrointestinal proteases. Due to incomplete degradation in the gastrointestinal tract, fairly long gluten peptides enter the small-intestinal lumen and come into contact with the mucosal epithelium, and in celiac disease patients this encounter launches deleterious downstream effects. Enzyme supplement therapy using either bacterial or fungal endopeptidases or proteases from germinating cereals has been proposed to promote complete digestion of prolamins and destroy disease-inducing gluten peptides. A major advantage of these glutenases is that they work in the lumen of the small intestine and do not themselves take part in the immunological cascade of events in the lamina propria, thus being unlikely to cause harmful side effects to the host. Studies to test this rationale, e.g. with Aspergillus niger prolyl endoprotease and a combination enzyme product ALV003, are already ongoing. The development of a novel medication for celiac disease is still in its early days, and thus the conventional dietary treatment will hold its place for the time being.

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“…Mixtures of germinating wheat proteases and purified prolyl endopeptidases (PEPs) have been reported to hydrolyse proline-rich gluten and to reduce their T cell toxicity in vitro (39,40). PEPs from different bacterial (FM, MX, and SC PEP from Flavobacterium meningosepticum, Myxococcus xanthus, and Sphingomonas capsulata, respectively) and fungal species (AN PEP from Aspergillus niger) have been extensively studied (41,42).…”

Section: Oral Enzyme Supplementationmentioning

confidence: 99%

Celiac Disease: A Challenging Disease for Pharmaceutical Scientists

2012

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Celiac disease (CD) is an immune-mediated enteropathy triggered by the ingestion of gluten-containing grains that affects~1% of the white ethnic population. In the last decades, a rise in prevalence of CD has been observed that cannot be fully explained by improved diagnostics. Genetic predisposition greatly influences the susceptibility of individuals towards CD, though environmental factors also play a role. With no pharmacological treatments available, the only option to keep CD in remission is a strict and permanent exclusion of dietary gluten. Such a gluten-free diet is difficult to maintain because of gluten's omnipresence in food (e.g., additive in processed food). The development of adjuvant therapies which would permit the intake of small amounts of gluten would be desirable to improve the quality of life of patients on a glutenfree diet. Such therapies include gluten-degrading enzymes, polymeric binders, desensitizing vaccines, anti-inflammatory drugs, transglutaminase 2 inhibitors, and HLA-DQ2 blockers. However, many of these approaches pose pharmaceutical challenges with respect to drug formulation and stability, or application route and dosing interval. This perspective article discusses how pharmaceutical scientists may deal with these challenges and contribute to the implementation of novel therapeutic options for patients with CD.

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Enzymatic detoxification of gluten by germinating wheat proteases: Implications for new treatment of celiac disease

Abstract: Germinating wheat enzymes reduce the toxicity of wheat gliadin in vitro and ex vivo. Further studies are justified to develop an alternative therapy for celiac disease.

Cited by 50 publications

References 40 publications

“Eat as If You Could Save the Planet and Win!” Sustainability Integration into Nutrition for Exercise and Sport

“Eat as If You Could Save the Planet and Win!” Sustainability Integration into Nutrition for Exercise and Sport

Novel Treatments for Celiac Disease: Glutenases and Beyond

Celiac Disease: A Challenging Disease for Pharmaceutical Scientists

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