The study combined two biomarkers: the quantification of eye movements and the measurement of proteins such as neurofilament and alpha-synuclein in cerebrospinal fluid, to improve the early diagnosis of PSP, a rare neurodegenerative disease, but one that is particularly complex to diagnose in its early stages. The results have been published in the journal Movement Disorders, the leading international journal in the field of Parkinson's disease and movement disorders.
The study, coordinated by the IDIBAPS “Parkinson’s Disease and Other Neurodegenerative Movement Disorders: Clinical and Experimental Research” research group, analysed this cohort of 131 people with suspected PSP from various hospitals in the province of Barcelona, who were centrally assessed at the Hospital Clínic. A comparison group of healthy participants and patients with Parkinson's disease was also included.
Biomarkers that detect the disease before clinical symptoms appear
One of the most significant advances of the research is the identification of biomarkers capable of reliably differentiating PSP from other conditions with similar symptoms, even in patients with symptoms and signs so early that the diagnosis is highly uncertain. The results show that the quantitative study of eye movements—especially the speed and amplitude of saccadic movements—and the presence of elevated levels of neurofilament as well as the normality or slight alteration of alpha-synuclein in the cerebrospinal fluid can anticipate the diagnosis when the usual neurological examination only allows for a low suspicion of it.
These biomarkers, explains Yaroslau Compta, an investigator at IDIBAPS and leader of the study, could help to enrol patients in clinical trials at earlier stages of the disease, a time when therapies have more potential to be beneficial, as the neurodegeneration is less advanced.
Twenty percent of patients present a molecular signature similar to Parkinson's
The study also sheds new light on the presence of co-pathologies. Through a pioneering assay that detects the presence of alpha-synuclein aggregates in the cerebrospinal fluid—a protein associated with Parkinson's disease—the team has observed that 20% of people with PSP also present this molecular signature, albeit with a lower intensity. In other words, despite having PSP, they share a molecular signature with Parkinson's disease, a fact that will need to be taken into account when designing, stratifying and interpreting clinical trials for this disease.
Predicting survival to improve clinical care
Furthermore, the research team has confirmed that factors such as the clinical manifestations presented by patients or neurofilament levels in the cerebrospinal fluid are useful for predicting patient survival. Having reliable prognostic tools is essential for planning clinical follow-up and better guiding families, explains Cèlia Painous, a co-investigator in the study.
