Researchers Report a Possible Association Between ALS and Gluten Sensitivity

Researchers at Tel Aviv Medical Center, Tel Aviv University and Rabin Medical Center in Israel discovered a possible link between amyotrophic lateral sclerosis (ALS) and sensitivity to gluten. The study was recently published in the journal JAMA Neurology and is entitled “Transglutaminase 6 Antibodies in the Serum of Patients With Amyotrophic Lateral Sclerosis.”

ALS is a progressive neurodegenerative disease, characterized by the gradual degeneration and atrophy of motor neurons in the brain and spinal cord that are responsible for controlling voluntary muscles, such as the ones related to movement, speaking, eating, and even breathing. ALS patients may become totally paralyzed and the majority of patients die due to respiratory failure. There is no cure for the disease.

Celiac disease is a hereditary, autoimmune disorder of the small intestine characterized by pain, discomfort, chronic constipation and diarrhea, anemia and fatigue. The disease is caused by a reaction to gluten (a protein found in wheat, rye and barley), where the body mounts an immune response that attacks the small intestine, compromising proper nutrient absorption.

Interestingly, it has been reported that gluten sensitivity can also induce neurologic manifestations with or without gastrointestinal symptoms, and many of these patients have antibodies against a brain enzyme called tissue transglutaminase 6 (TG6). TG6 antibodies can be found in about 45% of celiac disease patients who also produce antibodies against transglutaminase 2 (TG2) upon gluten uptake. Two previous case reports have described individuals who were initially diagnosed with ALS and later with celiac disease, suggesting that gluten sensitivity can induce a syndrome similar to ALS.

The goal of this study was to determine the prevalence of antibodies related to celiac disease, including TG6 antibodies, in 150 ALS patients and 115 healthy controls in order to establish whether patients can develop neurologic symptoms associated to a gluten-related disorder that mimic ALS. None of the participants enrolled in the study had any known autoimmune or gastroenterologic disorder.

Researchers found that none of the ALS patients or healthy controls was positive for antibodies against TG2 or gluten-related peptides. 23 out of 150 ALS patients had a high concentration of antibodies against TG6, while in healthy controls only 5 out of 115 had anti-TG6 antibodies. TG6-positive ALS patients exhibited a typical ALS phenotype and rate of disease progression, not differing from TG6-negative ALS patients. TG6-positive healthy controls had no signs of any disease. Interestingly, ALS patients were found to be more likely to have celiac disease-specific genetic mutations than healthy controls.

The research team concluded that in certain cases, ALS might be linked to autoimmunity and gluten sensitivity, although the team emphasizes that this finding is preliminary and needs to be confirmed, “this is a preliminary and by now a single report” said the study’s senior author Dr. Vivian Drory in a news release. “I would be happy to see confirmation of our results from other centers,”

The team is currently testing the effects of a gluten-free diet in ALS patients who are positive for antibodies against TG6. Dr. Drory, however, advises that ALS patients should not adopt such diet at this point. “Patients should not be tempted to use a gluten-free diet without clear evidence for antibodies, because an unbalanced diet might harm,” said Dr. Drory. “Especially in ALS we know that maintaining a good caloric intake and weight improves prognosis. While one can achieve a good caloric intake with a gluten-free diet, this should be done only under dietician advice and in the specific patients in whom antibodies are detected.”