NAF Ataxia Research Studies Currently Underway

Armin Alaedini, PhD

Weill Medical College of Cornell University
Immune reactivity to synapsin in the ataxia associated with gluten sensitivity

Summary: Celiac disease is a complex autoimmune disease that is triggered by ingestion of gluten in genetically susceptible individuals. It is a common disease (prevalence of 1% in United States and Europe), which is associated with multiple extra intestinal manifestations. Cerebellar ataxia is among the most common and debilitating neurologic complications associated with gluten sensitivity. The associated ataxia has been suspected to have an autoimmune component, with gliadin playing a central role in the pathogenic mechanism. In preliminary studies, we have found that antibodies to gliadin cross-react with and bind to a major protein of the nervous system, called synapsin I. The synapsin I protein has a key role in the release of neurotransmitters in the nervous system. Our hypothesis is that such cross-reactivity of anti-gliadin antibodies against the synapsin I molecule plays a pathogenic role and is associated with neurologic manifestations, including cerebellar ataxia. We propose to test this hypothesis as follows: 1) To determine whether there is an association between anti-gliadin antibody cross-reactivity with synapsin I and presence of gluten sensitivity in ataxia patients, 2) To map the cross-reactive amino acid sequences of the synapsin I molecule, and 3) To determine whether the cross-reactive antibodies exhibit pathogenic characteristics that have potential for causing disease. The proposed studies are expected to shed light on how cerebellar ataxia may be associated with gluten sensitivity. They may also serve to provide a useful antibody marker for the diagnosis of gluten sensitivity-associated cerebellar ataxia, and offer a rationale for examining the efficacy of therapies that target autoimmune mechanisms in affected patients.