I was recently asked whether following The Paleo Diet can help to treat individuals diagnosed with Huntington’s Disease (HD). HD is a neurodegenerative illness in which brain and nervous tissue are affected. Recent molecular advances suggest that increased expression of an enzyme called transglutaminase is likely involved in eliciting the disease in genetically susceptible people, and that transglutaminase inhibitors may be therapeutic in tissue cultures and animal models. Further, at least one study done in 2004 showed that 44% of HD patients maintained antibodies to gliadin, the storage protein found in gluten containing grains (wheat, rye, barley). Human studies have demonstrated that wheat and gluten consumption upregulates, or increases the expression of transglutaminase in a variety of human tissues, which can be reversed by gluten-free diets. To date, while there are no clinical trials evaluating gluten-free or Paleo diets in HD patients, I am aware of at least one anecdotal case of a young HD patient whose symptoms, as measured by MRI, remitted after following a gluten-free/Paleo diet. I don’t want to give HD patients false hope, nevertheless there are no known nutritional dangers to following The Paleo Diet.
I shared the notion of transglutaminase upregulation autoimmunity via wheat consumption with Trevor Connor, my graduate student in HES and Nutrition at the Colorado State University. We worked out the potential mechanism of how wheat/gliadin upregulates transglutaminase and may predispose genetically susceptible individuals to Huntington’s Disease.
Huntington’s Disease is genetic. If a genetic mutation in the gene that codes for Huntington Protein is identifiable, you have this mutation and will develop Huntington’s Disease.
The mutant Huntington Protein has a “repeat.” The glutamine sequence starts multiplying and lengthening the protein. This repeat serves no purpose, but Huntington’s Disease is considered active at over 36 repeats. People with active Huntington’s Disease have a mutant protein in the brain that starts aggregating by binding to itself and other proteins. The aggregates then bind to neurons and kill them.
Scientists are focusing on trying to prevent the repeat and aggregation. However, we found a critical study where they knocked out tissue transglutaminase in Huntington’s mice. Even though aggregation was severe in these mice, disease onset was delayed and if it did develop, it was less severe.
It was our belief that this same mechanism of gliadin binding to tissue transglutaminase (tTG) in Celiac’s Disease, is the environmental trigger in Huntington’s disease. It’s the gliadin-tTG complex that is influencing pathogenesis, or mechanism by which Huntington’s Disease is caused.
Immune Activation: In another important set of studies, HLA-DR, a heterodimeric cell surface glycoprotein, expression was increased by gluten consumption. In active Huntington’s subjects, HLA-DR activity was so strong in their disease tissue, it was visible with the human eye after staining.
In the same way that gluten breaks down the barrier of the gut, there is some evidence that gluten can open up the blood-brain barrier and allow the gliadin-tTG complex to enter protected neural regions and activate the Huntington aggregates.
Learn more: Connor, Trevor B.“A Potential Dietary-Based Environmental Trigger for Huntington’s Disease” Thesis. Department of Health and Exercise Science, Colorado State University, 2010.
Loren Cordain, Ph.D., Professor Emeritus