Refining the clinical diagnosis of MSA-C and MSA-P using olfactory mucosa and skin samples

Multiple system atrophy (MSA) is a rare and devastating brain disease that can manifest in two different forms: MSA-P, where symptoms include slowness of movement, rigidity, balance issues, and autonomic failure; and MSA-C, characterized by gait and balance problems, difficulty in walking, limb coordination problems and jerky speech. Both pathologies are characterized by the cerebral accumulation of a pathological protein named alpha-synuclein. Definite diagnosis can only be confirmed through specific examinations of brain tissue. Clinical diagnosis is particularly challenging because the symptoms can be similar to other diseases, collectively named alpha-synucleinopathies, which include Parkinson’s (PD) and dementia with Lewy bodies (DLB), especially in the early stages.

Accurate differential diagnosis between MSA-P, MSA-C and other alpha-synucleinopathies is critical for selecting the right patients for clinical trials and developing more effective treatments. The main objective of the study is to leverage our expertise in analyzing olfactory mucosa and skin samples with advanced and sensitive techniques to discover new peripheral biomarkers specific to MSA. In particular, by studying samples from extensively characterized MSA-C and MSA-P patients already available at Fondazione IRCCS Istituto Neurologico Carlo Besta, we will assess the effectiveness of our analytical approach in improving the clinical diagnosis of MSA and recognize disease phenotypes. Indeed, we seek to support the standard clinical and instrumental evaluations using a biologically-based approach, overcoming the current limitations of clinical interpretations.

Our study could also contribute to a deeper understanding of the role of pathological alpha-synuclein in the progression of the disease. By shedding light on this aspect, we hope to advance knowledge and pave the way for more targeted therapies in the fight against this devastating disease.