Patients with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) encounter symptoms that affect their walking ability. Among these, they show abnormal tensing of the muscles (spasticity), which partly derives from the disruption of a bundle of fibers responsible for voluntary motion (the corticospinal tract). Damage to the corticospinal tract has been sporadically reported in ARSACS, but we do not know which portion of the fibers is damaged nor if higher degree of damage corresponds to worse symptoms. In this study we will assess the integrity of the corticospinal tract using a novel approach, based on the examination of proteins presents in peripheral blood and Magnetic Resonance Imaging of the brain. We will use data from a large group of ARSACS patients, available from the PROSPAX project, a multi-center European study that includes clinical, molecular and imaging data. We will reconstructs for each subject the corticospinal tract, investigating whether alterations at the microstructural level of the fibers that constitute this bundle are associated to markers of fiber damage measured in peripheral blood and to the degree of clinical impairment. If, as we hypothesize, spasticity will be associated to specific microstructural abnormalities of the corticospinal tract, which, in turn, will be associated to a marker of fiber damage measurable in the blood, we will have identified one (or more) biomarkers that can be obtained from a non-invasive brain MRI and that can be used not only to monitor brain damage and disease progression but, in the future, to monitor response to therapies.
Project funded by the Organizzazione di volontariato (ODV) with the support from the Fondazione Telethon.
Duration: one year
Dr. Sirio Cocozza
University of Naples Federico 11