Researchers from the IDIVAL neurodegenerative diseases group and the CSUR group of HUMV hereditary ataxias and paraplegia, led by Dr. Jon Infante, have participated in an international multicenter study designed to identify preclinical and progression biomarkers in the most frequent form of autosomal dominant cerebellar ataxia, SCA3. The identification of accurate, reliable and easily accessible biomarkers is one of the necessary requirements for the development of clinical trials with the best guarantees of success.
In the study published in the journal EMBO Molecular Medicine, serum concentrations of light neurofialments (NfL) and phosphorylated heavy neurofilaments (pNfH) were studied in two cohorts of 250 patients with SCA3-type ataxia and controls. Subjects in presymptomatic stages of the disease were also represented in these cohorts. The same experiment was carried out on a transgenic mouse model. NfL and pNfH levels were found to be increased in SCA3 patients and also in preclinical stages. Serum NfL levels were found to correlate with both disease severity and longitudinal progression. It is concluded from this study that neurofilaments in blood can be an accessible biomarker in patients with SCA3, associated with early neuropathological changes and be used as a biomarker of progression and potentially response to treatment in clinical trials.
The group of neurodegenerative diseases of IDIVAL and the CSUR of ataxias and inherited paraplegias of the HUMV have been part of a European consortium for more than two decades that seeks to define the natural history of autosomal dominant cerebellar ataxias, as well as to build cohorts prepared for the laying clinical trials underway. In the framework of this consortium, various European projects (EUROSCA, RISCA, ESMI) have been financed, with the participation of HUMV-IDIVAL.
