Celiac disease is an autoimmune condition in which the immune system forms antibodies and reacts to the presence of gluten in the intestine. The result is an inflammatory reaction and, ultimately, damage to the lining of the intestine. This, in turn, causes symptoms such as diarrhea, cramping, weight loss, anemia, and malabsorption. Associated long term risks include: cancer of the small intestine, lymphoma, osteoporosis, and other micronutrient deficiencies.
Celiac disease can present in childhood; however, this form of celiac disease is rare. More commonly, celiac disease presents in adulthood, at approximately 40-50 years of age. There is no cure for celiac disease, sufferers can only make use of preventative measures by way of a gluten-free diet. Gluten is present in wheat, rye, and barley, in addition to many processed foods. Restriction to a gluten-free diet can negatively impact on quality of life by restricting food choices and social activities, and can impact financially due to the added expense of purchasing gluten free products. Moreover, even when adhering to a strict gluten-free diet, there is a subset of patients that will have persistent symptoms. There is, therefore, a need for continued research and development of treatments for celiac disease. Below is a summary of some of the emerging therapies currently in clinical trials for Celiac Disease.
A Phase 1 safety and efficacy study is being conducted by Igy Inc. at the University of Alberta, Canada using AGY, an antibody against gluten. The antibody IgY is produced from the egg yolks of super immunized hens. The capsule form of IgY is called AGY. The study participants will take AGY capsules with their meals for 4 weeks. After the 4 week study period, antibody levels, patient symptoms, and quality of life will be assessed. The outcomes measured by the trial will be general safety, symptoms, and health related quality of life.
Humanized Mik-Beta-1 Monoclonal Antibody
A Phase 1 safety and efficacy trial is currently recruiting at the University of Chicago and Mayo Clinic, Rochester, Minnesota. The study will investigate the potential for Hu-Mik-B1 in the treatment of refractory celiac disease. Refractive celiac disease is a rare form of celiac disease that persists despite a strict gluten free diet, with serious complications, including: nutritional deficiencies, weight loss, and malabsorption. There is currently no effective treatment for refractory celiac disease. Hu-Mik-B1 is an antibody targeted to IL-15 signaling. It is this signaling pathway that is believed to be responsible for the intestinal damage associated with refractory celiac disease. Hu-Mik-B1 is not yet FDA approved; however, it has been approved for use in this clinical trial.
A recent study conducted in Finland showed promising results, including a reduction of small intestinal damage in celiac patients taking ALV003. Alvine Pharmaceuticals is conducting a phase 2 safety, efficacy, and dose ranging study of the effects of ALV003 on the lining of the small intestine in patients with celiac disease. The study is being conducted in 66 study locations across the US, Canada, Finland, Ireland, Norway, and the UK. ALV003 is a mixture of two gluten-specific proteases, taken orally, that have been shown to digest gluten. Participants will continue on a gluten free diet while taking ALV003. The study will assess morphological changes in the small intestine 12 weeks following treatment. In addition, symptomatic changes and quality of life will be measured during the 12 week period.
Mooney, PD,Hadjivassiliou, M, Sanders,DS“Clinical Review: “Coeliac Disease.” BMJ 2014;348:g1561
Clinicaltrials.gov “Oral AGY for Celiac Disease” Available from: http://www.clinicaltrials.gov/ct2/show/NCT01765647?term=coeliac+disease&recr=Open&no_unk=Y&rank=9Last Accessed: April 15, 2014.
Clinicaltrials.gov “Phase I Study of Humanized Mik-Beta-1 Monoclonal Antibody (Hu-Mik-Beta-1)” Available from: http://www.clinicaltrials.gov/ct2/show/NCT01893775?term=coeliac+disease&recr=Open&no_unk=Y&rank=16Last Accessed: April 15, 2014.
Clinicaltrials.gov “Evaluation of the Efficacy and Safety of ALV003 in Symptomatic in Celiac Disease Patients” Available from: http://www.clinicaltrials.gov/ct2/show/NCT01917630?term=coeliac+disease&recr=Open&no_unk=Y&rank=11Last Accessed: April 15, 2014.
“Alvine’s Lead Drug Candidate: ALV003”Available from:http://www.alvinepharma.com/alv003/Last Accessed: April 15, 2014.
Image courtesy of adamr / FreeDigitalPhotos.net
Written by Deborah Tallarigo, PhD