Focusing on Mithocondrial Dysfunction in Multiple Sclerosis: The Role of GDF-15 and FGF-21 as Prognostic Biomarkers
Vincenzo Carlomagno1, Alessandra Cicia1, Assunta Bianco2, Matteo Lucchini2, Massimiliano Mirabella2
1Catholic University of Sacred Heart, Rome, 2Catholic University of Sacred Heart, Rome; Fondazione Policlinico Gemelli IRCCS Rome
Objective:
This is a single-center retrospective study where we examined the serum and cerebrospinal fluid (CSF) concentrations of mitochondrial dysfunction biomarkers (GDF-15 and FGF-21) in Multiple Sclerosis (MS) patients.
Background:
In MS, several biomarkers from biological fluids have been proposed to assist with diagnosis, predict disease progression, and assess treatment response. Recently, there has been growing interest in mitochondrial dysfunction biomarkers.
Design/Methods:
This study included patients with Relapsing and Progressive MS (RMS and PMS), as well as those with other inflammatory (OIND) and non-inflammatory neurological disorders (ONIND). Using an ultrasensitive automated immunoassay on the Ella® platform, we analyzed the levels of these biomarkers in 143 patients: 104 with RMS, 10 with PMS, 17 with OIND, and 12 with ONIND.
Results:
CSF FGF-21 levels were below the detection limit and excluded from further analysis. PMS patients exhibited the highest serum and CSF concentrations of GDF-15, as well as the highest serum FGF-21 levels. No significant differences were observed between RMS and OIND/ONIND groups. In RMS patients, we further analyzed the relationship between biomarker levels and disease activity, dividing them into high and low groups based on mean biomarker concentration in ONIND. High CSF GDF-15 levels were associated with increased disability progression, but a reduced risk of radiological activity (new/enlarging T2/FLAIR lesions).
Conclusions:
Our findings suggest that mitochondrial dysfunction biomarkers are elevated in PMS compared to RMS and other neurological conditions. Furthermore, in RMS patients, higher CSF GDF-15 levels are linked to greater clinical disability, though not to increased inflammatory activity. These biomarkers hold promise for better understanding and managing chronic inflammatory diseases like MS, and future research should explore their role in MS pathogenesis and potential therapeutic strategies targeting mitochondrial function.
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